Surgical treatment and its consequences expose patients to stress, and here we investigated the importance of the psychological component of postoperative pain based on reports in the clinical literature.Postoperative pain remains a significant clinical problem. Increased pain intensity with increased demand for opioid medication, and/or a relative unresponsiveness to pain treatment was reported both when the analgesia was administered by means of conventional nurse injection regimes and patient-controlled analgesia (PCA). Both the quality of the analgesia, and the sensitivity of postoperative models for assessing analgesic efficacy could be significantly influenced.The findings could be explained by increased penetration of an algesic anxiety-related nocebo influence  relative to its analgesic placebo counterpart. To counteract this influence, the importance of psychological effects must be acknowledged, and doctors and attending nurses should focus on maintaining trustful therapist-patient relationships throughout the treatment period. The physical mechanism of anxiebo should be further explored, and those at risk for anxiebo better characterized. In addition, future systemic analgesic therapies should be directed towards being prophylactic and continuous to eliminate surgical pain as it appears in order to prevent the anxiebo effect.Addressing anxiebo is the key to developing reproducible models for measuring pain in the postoperative setting, and to improving the accuracy of measurements of the minimum effective analgesic concentration.Anxiebo and placebo act as counterparts postoperatively. The anxiebo state may impair clinical analgesia and reduce the sensitivity of analgesic trials. Ways to minimize anxiebo are discussed. Continterpart -6  and anticipatory anxiety are important factors in determining whether somebody will be a placebo or anxiebo responder -9, and mThe effects of anxiebo and placebo can be clearly visualised on PET scans of the brain . During Reviews of analgesic trial outcomes have indicated that the degree of pain relief obtained may range between 0 and 100 per cent both for placebo and active drug patients ,13. A plA combination of nonopioid analgesics and opioids is most often used to achieve postoperative analgesia, and the opioids are frequently administered by nurse-administered injections. Delay between need and injection constitutes the major problem with this approach . ClassicSeveral studies indicate that a significant fraction of PCA patients experiences moderate or severe pain ,3. RegioStudies into the use of PCA lend themselves also to further evaluation because of the considerable use of PCA as a research technique for assessing analgesic efficacy. There are many indications in the literature that PCA functions well as an analgesic method and that the patient-control concept is accepted by the patients. However, the question of control may be difficult to assess in a clinical situation involving an element of dependence. Recent reports show that many PCA patients do not recognize themselves as being in control of their treatment, and they may experience side effects and fear on utilization that limit their ability to control pain ,22. It iIn PCA, it is logical that the combination of an anxiebo-induced decrease in opioid sensitivity and an increase in the rate of self-administration as part of a coping reaction to anxiebo may in certain patients lead to pronounced overuse of morphine that is unrelated to the need for analgesia.vs patient) throughout the treatment period should be recognized. Assuming that anxiebo could be eliminated clinically, the placebo state would be more prevalent, although its maximal overall influence in terms of improving the outcome of opioid treatment cannot yet be judged.The observations above indicate that both nurse injection regimes and PCA may produce signs of anxiebo characterized by increased pain intensity with increased demand for opioid medication, and/or a relative unresponsiveness to pain treatment, which may last for days Figure . AvoidinIt is likely that the direct caregiver-patient relationship in nurse injection regimes can be used to better advantage, and minimizing stressful break-through pain should be emphasized. With regard to PCA, we do not doubt its role when applied in a suitable, psychologically supportive environment, but the method is more complex than generally thought. For those patients who do not adapt to the control concept, and respond with signs of anxiebo, extra support may be required or alternative treatment should be sought.Conceptually, it would appear advantageous to direct future systemic analgesic therapies towards being prophylactic and continuous  rather than reactive and intermittent. By analogy, the use of continuously acting psychotropic drugs that specifically counteract elements of the anxiety state may be effective in patients who respond poorly to analgesia.The mechanisms underlying anxiebo should be further explored and other measures aimed at reducing anxiebo should be examined. In particular, further efforts should be devoted to defining patient groups and individuals that are especially at risk. This may be done by developing easily applicable scales for identifying at-risk patients preoperatively, and by preparing these patients with suitable information. Techniques should be sought which allow postoperative diagnosis of anxiebo. We suggest that perceived expectancy of future pain as opposed to subjective estimates of current pain may be a parameter of interest for better predicting a patient's risk for the anxiebo effect.While the drug placebo effect is regularly accounted for in clinical trials, the effect of its anxiebo counterpart is not. It appears likely that trial assay sensitivity is reduced with variable penetration depending on the specific therapeutic circumstances of the individual study. Anxiebo may result in false-negative or borderline results, as indicated above for PCA models. Such systemic errors are not removed by simply increasing the size of the trial. The key to a reproducible, sensitive model is the proper handling of individual factors interacting within the psychological context, with respect for the therapist-patient relationship. Education and support to personnel handling the patients postoperatively seems to be the critical factor. Optimally, the anxiebo effect should be accounted for, perhaps by conducting a preliminary sensitivity test using a drug (such as morphine) with known analgesic effects.Since patients or patient groups receiving PCA may not titrate their opioid dosage Figure , it follThe importance of psychological reactions are commonly acknowledged in postoperative analgesia, but the way these reactions express themselves and the degree of disturbance they may cause by producing anxiebo rather than placebo states are at present incompletely considered. Maintaining trustful therapist-patient relationships throughout the treatment period is very important. Future systemic analgesic therapies should be directed towards being prophylactic and continuous to eliminate surgical pain as it appears so as to prevent the anxiebo effect. The physical mechanism of anxiebo should be further explored, and more effort made to define patient groups and individual patients especially at risk. Addressing anxiebo is of importance also in the development of reproducible models for assessing analgesic efficacy in the postoperative setting, and may improve the accuracy of measurements of the minimally effective analgesic concentration.The author(s) declare that they have no competing interests.All three authors participated in the design and preparation of the manuscript, and all approved the final draft.The pre-publication history for this paper can be accessed here:


Patients with moderate to severe malignancy-related pain frequently require the use of opioid pharmacotherapy. Unfortunately, many cancer patients continue to be prescribed subtherapeutic doses of pain medications resulting in undo suffering and diminished quality of life. The choice of analgesic pharmacotherapy should be individualized and based on the intensity and etiology of pain reported by the patient. Health care providers must be able to readily quantify the relative analgesic potency when converting from one opioid to another or from one route of administration to another. Transdermal fentanyl is effective and well tolerated pharmacotherapy for the cancer pain patients. However, clinicians need to be cognizant that the U.S./U.K. manufacturer's recommendations for equilalagesic dosing of transdermal fentanyl may result in initial doses that produce subtherapeutic levels and unrelieved pain in some patients. A more aggressive dosing algorithm for transdermal fentanyl using a 2:1  conversion ratio that considers both a review of the literature and clinical experience should help clinicians individualize cancer pain pharmacotherapy. Transdermal buprenorphine is now being prescribed in Europe and Australia for chronic and cancer pain management. Buprenorphine's mixed agonist/antagonist activity, dosage ceiling, and high affinity to the opiate receptor limits its use to those patients who do not already require large daily doses of opioids. Thus, buprenorphine may not be an appropriate medication for some patients with advanced unremitting cancer pain. Management of malignancy-related pain continues to be a major problem due to undertreatment and/or inadequate selection of adjunctive medications and other modalities combined with opioid therapy. Significant pain is reported in at least one-third of newly diagnosed oncology patients, and 65 to 85 percent of those with advanced disease ,2. A broA thorough pain assessment must be conducted on each patient. This assessment should include pain severity and etiology, age, extent of disease, previously effective and ineffective therapies, concurrent medical problems, and psychosocial status. It is important to note that the care plan for each patient must be individualized, regularly reassessed, and adjusted, if necessary, to maximize pain control and quality of life ,5,6. TheThe World Health Organization (WHO) pain management guidelines suggest that the choice of analgesic pharmacotherapy be based on the intensity of pain reported by the patient, not simply its specific etiology -10. OpioTable 1. Calculate the previous 24-hour analgesic requirements.2. Convert this amount to the equianalgesic oral morphine dose.3. Determine the calculated 24-hour oral morphine dose and corresponding transdermal fentanyl dose.4. Initiate treatment using this recommended dose, and titrate dosage upward  until analgesic efficacy is attained.Unfortunately, the aforementioned manufacturer's recommended dosing conversions for transdermal fentanyl provided in Table There have been four case reports in the literature documenting withdrawal syndromes associated with conversion from oral opioids to transdermal fentanyl ,25. WithCancer patients require an aggressive approach to their pain management and the initial dosing transdermal fentanyl. Care must be taken to avoid subtherapeutic dosing that can compromise patient care and result in uncontrolled pain during the initial conversion and titration period. The conversion table supplied by the manufacturer in Germany Table  is much A multi-center trial conducted by Donner et al supports the safety and efficacy of the German recommended 2(mg/day):1(mcg/hr) oral morphine to transdermal fentanyl ratio . The stuA more recent study of 1,828 cancer patients who were either opioid naïve, taking codeine or morphine for their pain used an average 3(mg/day):1(mcg/hr) conversion ratio for enrollment into each study group . The resEvaluations as to whether the initial starting dose of transdermal fentanyl is providing adequate pain relief should be conducted during the first 72 hours after initiation. If the patient requires more than two doses of breakthrough medication over a 24-hour period for adequate pain relief, than consideration should be given to increase the fentanyl patch dose. At low doses of opioids, the patch is normally increased in 25 mcg per hour increments. It may be increased in increments of 50 mcg per hour if the severity of the pain, number of breakthrough doses required, and total dose of transdermal fentanyl needed for adequate relief warrants this level of increase. Fifty (50) mcg incremental dose increases should only be employed in patients that are not opioid naïve and where a 50 mcg escalation represents and appropriate percentage of the entire daily opioid dose. The optimal dose of transdermal fentanyl should be based on an ongoing evaluation of the level of pain relief achieved and the amount of breakthrough medications utilized. It is important to note that it can take from 12 to 18 hours to reach a clinical relevant serum level after initial patch placement. Consistent serum levels are achieved after 16 to 20 hours, and steady state is attained at about 72 hours [Upon initial dosage titration, and in order to minimize the risk of opioid withdrawal during the first 16 hours of transdermal fentanyl therapy, patients should be instructed to take the prescribed immediate release opioid every 3 to 4 hours . The dosBreakthrough pain should be treated with medications that are simple to administer, offer rapid pain relief, and have a reasonably short half-life . ImmediaGood adhesion of the fentanyl patch to the skin is essential for maximum efficacy, therefore patients must be instructed on the proper technique for patch application . Hair onFor the majority of patients, the analgesic effect of fentanyl will last for 72 hours and a new patch applied after that time. Changing fentanyl patches more often than every 48 hours is not recommended. Many clinicians recommend increasing the dosage rather than shortening the dosing interval. However some patients may find that the effect begins to decline after 48 hours and lasts only for around 60 hours ,33. In tThe overall tolerability of transdermal fentanyl is very good. The most frequently observed adverse effects include nausea, vomiting and constipation ,34,35. CHypoventilation (defined as respiratory rates of less than 8 breaths per minute or a pC02 greater than 55mm Hg) was reported in three (2%) of the 153 patients with cancer pain during the pre-marketing trial . HoweverPatients should be instructed to refrain from driving or operating machinery immediately following the initiation of transdermal fentanyl, or after any dosage increase ,22. PatiConcomitant use of other centrally acting depressants such as sedatives, other opoids, hypnotics, phenothiazines, tranquillizers, skeletal muscle relaxants, anesthetics, sedating antihistamines, and alcohol can cause hypoventilation, acute sedation, or hypotension in patients taking transdermal fentanyl . It is aBuprenorphine, a centrally acting opioid analgesic, is now being prescribed in Europe and Australia for chronic and cancer pain management -44. BuprTransdermal buprenorphine is available with release rates of 35, 52.5, and 70 micrograms per hour which corresponds to daily doses of 0.8, 1.2, and 1.6 milligrams of buprenorphine, or approximately 60, 90, and 120 milligrams per day equivalent of oral morphine, respectively -41,44. SBuprenorphine TDS has been shown to be quite effective against chronic, severe pain in three multicenter, randomized, double-blind, placebo-controlled studies -47. PatiTransdermal delivery of buprenorphine provides for a slower increase in serum concentration and no peak-and-trough effects as seen with the sublingual route of administration. As a result, there are fewer adverse events reported when using the transdermal delivery system for this medication -44. TranOf very important note is that because buprenorphine is a mixed opioid agonist/antagonist, it does have a dosage ceiling ,39. TherBased on the currently available clinical trial data, transdermal buprenorphine is a valuable alternative to other available opioids in many chronic pain conditions. However, despite the positive data presented in these four clinical trials, more controlled studies are needed to determine the place of transdermal buprenorphine among current treatment strategies for chronic and cancer pain, and to explore if and whether transdermal buprenorphine would be of any value in the treatment of difficult pain conditions such as neuropathic pain.Many pharmacotherapeutic choices are available for the management of cancer pain. HCPs must be able to readily quantify the approximate relative analgesic potency when converting from one opioid to another and from one route to another. Transdermal formulations of fentanyl and burprenorphine are very useful pharmacotherapy for the cancer patient experiencing moderate to severe pain. Buprenorphine's mixed agonist/antagonist activity, dosage ceiling, and high affinity to the opiate receptor limits its use to those patients who do not already require large daily doses of opioids. Thus, buprenorphine may not be an appropriate medication for some patients with advanced unremitting cancer pain. Clinicians need to be aware that the relative opioid conversion tables commonly utilized are often based on the results of single-dose studies and frequently underestimate the dosage required for the cancer pain patient. Generally, a more aggressive approach to converting a patient to transdermal fentanyl may be warranted in the cancer patient. Care must be taken to individualize each patient's pain management in order to prevent opioid withdrawal and substantially reduce the undertreatment and overtreatment of cancer-related pain and its associated negative impact on patients' quality of life.


Facial pain may be divided into several distinct categories, each requiring a specific treatment approach. In some cases, however, such categorization is difficult and treatment is ineffective. We reviewed our extensive clinical experience and designed an algorithmic approach to the treatment of medically intractable facial pain that can be treated through surgical intervention.Our treatment algorithm is based on taking into account underlying pathological processes, the anatomical distribution of pain, pain characteristics, the patient's age and medical condition, associated medical problems, the history of previous surgical interventions, and, in some cases, the results of psychological evaluation. The treatment modalities involved in this algorithm include diagnostic blocks, peripheral denervation procedures, craniotomy for microvascular decompression of cranial nerves, percutaneous rhizotomies using radiofrequency ablation, glycerol injection, balloon compression, peripheral nerve stimulation procedures, stereotactic radiosurgery, percutaneous trigeminal tractotomy, and motor cortex stimulation. We recommend that some patients not receive surgery at all, but rather be referred for other medical or psychological treatment.Our algorithmic approach was used in more than 100 consecutive patients with medically intractable facial pain. Clinical evaluations and diagnostic workups were followed in each case by the systematic choice of the appropriate intervention. The algorithm has proved easy to follow, and the recommendations include the identification of the optimal surgery for each patient with other options reserved for failures or recurrences. Our overall success rate in eliminating facial pain presently reaches 96%, which is higher than that observed in most clinical series reported to dateThis treatment algorithm for the intractable facial pain appears to be effective for patients with a wide variety of painful conditions and may be recommended for use in other institutions. The term "facial pain" encompasses variety of clinical conditions ranging from very common  to less common  and quite rare  Table . AlthougAs to the available procedures for treatment of the medically intractable facial pain, the spectrum of interventions includes a wide variety of procedures starting from non-destructive approaches (such as microvascular decompression (MVD) of trigeminal and other cranial nerves) to percutaneous interventions (radiofrequency (RF) gangliolysis, glycerol injection, balloon compression) to less invasive destructive procedures (stereotactic radiosurgery) and to neuromodulation surgeries  as well as central destructive surgeries  Table .Recently, two in-depth clinical articles presented different modalities used in treatment of facial pain ,6. One oSince our clinical practice attracts a large number of patients with facial pain, we decided to create an algorithm for its surgical treatment and summarize applicability of such algorithm based on degree of pain relief and patient satisfaction. The analysis presented here was derived from a prospective study of patients with facial pain that was approved by our Institutional Review Board few years ago .The algorithm for treatment of medically intractable facial pain that we use is based on taking into account underlying pathological processes, the anatomical distribution of pain, pain characteristics, the patient's age and medical condition, associated medical problems, the history of previous surgical interventions, and, in some cases, the results of psychological evaluation. The largest part of our algorithmic approach to facial pain is, not surprisingly, dedicated to treatment of trigeminal pathology, including TN and other disorders of trigeminal system . Surgeries for migraine and other headache syndromes are currently in an early research phase; dental and TMJ problems rarely come to neurosurgical attention but should be kept as a part of differential diagnosis in patients with chronic facial pain; non-trigeminal disorders  are significantly less common (at least in our practice) and, in most cases, may be diagnosed by specific distribution of pain that involves ear, throat, occiput, neck alone or in addition to facial territory.Importance of detection of the underlying pathological processes may be illustrated by difference in surgical management of various possible causes of symptomatic (secondary) TN  that would require definitive treatment (such as tumor resection) in order to obtain pain control , or sympPatient's age and medical condition become important in algorithmic approach to facial pain, particularly in those diagnosed with TN, since MVD requires craniotomy and carries certain risk of complications related to surgery and general anesthesia. This risk increases with the patient's age and associated co-morbidities. Therefore, for older and medically unfit patients, preference is given to less invasive percutaneous destructive procedures and stereotactic radiosurgery (SRS).Although MVD has been shown effective in elderly TN patients and those with secondary TN from MS, we do not routinely suggest it for these patient categories. This approach may reflect our institutional bias, but in the authors' opinion, the lower yield of MVD in MS and higher risk of complications in elderly patients undergoing MVD do not justify considering MVD as the first choice in these particular situations.nd or 3rd division of the trigeminal nerve (maxillary and mandibular nerves) due to somewhat higher risk of corneal hypesthesia or anesthesia with resultant keratitis and corneal abrasions if 1st branch  fibers are targeted by RF energy.Among percutaneous destructive procedures that are used for TN, each of three modalities  may be used for idiopathic (TN types 1 and 2) and symptomatic (secondary) TN, but in our opinion, RF gangliolysis works best in those TN patients that present with pain in 2Therefore, balloon microcompression in our algorithm is reserved for patients with TN whose pain involves distribution of the first trigeminal branch  with or without other branches.SRS with Gamma Knife (or linear accelerator) is reserved for those patient with TN types 1 and 2  who prefer to avoid any mechanically invasive procedures (open or percutaneous interventions) and only if they can tolerate their pain for 1–3 months that are required for pain relief after radiosurgery.The nature of pain and results of neurological evaluation allow one to diagnose other pain syndromes involving the face and differentiate them from classic TN (TN type 1). For example, presence of constant pain, lack of response to carbamazepine, and associated numbness would put the patient either into category of "atypical TN (ATN)" (if sharp and shooting pain is present) or "trigeminal neuropathic pain (TNP)" . Both of these conditions may be classified as TN type 2 (if the pain is idiopathic), true TNP  or trigeminal deafferentation pain  ,4. MVD fAtypical facial pain (AFP), on the other hand, does not follow clear anatomical distribution, frequently crosses midline, and, not surprisingly, almost inevitably correlates with presence of psychological aberrations. Patients with AFP do not improve with surgical interventions; therefore, it is recommended to avoid surgery and continue treatment with anticonvulsants and antidepressants as soon as the diagnosis is made.Other, less frequent pain syndromes, such as GPN , Eagle s1. If the patient has anatomical distribution of pain, determine if this distribution correlates with trigeminal territory or territory supplied by other nerves of face/head region ; if it is limited to trigeminal area, proceed to step #2; if other nerves are involved, proceed with step #13; if pain is non-anatomical in character, proceed with step #14.2. If the patient's pain is limited to trigeminal distribution, define if it has features of TN – sharp shooting (electric-shock like) pain, triggerable by touch, speech, cold wind, etc., responsive to oral carbamazepine, with spontaneous remissions, pain-free intervals – proceed with step #3; if any of the typical TN features are absent, but the majority of pain is sharp and shooting in nature, proceed with step #6; if the pain is in trigeminal distribution but is primarily constant and is associated with certain degree of sensory loss, proceed with step #9; obtain MRI of the brain in all of these cases to rule out mass lesions and demyelination.microvascular decompression (MVD) through suboccipital craniotomy, independently of the trigeminal branch involved.3. If the patient has TN type 1  – as documented by TN features and brain imaging negative for mass lesions in the cerebellopontine angle and demyelination – the procedure of choice is or if the patient prefers to avoid open surgical intervention, or if the pain recurred after MVD performed in the past, or if the brain imaging is suggestive of demyelination , and if the pain involves 3rd, 2nd or 2nd and 3rd branches, the procedure of choice would be percutaneous stereotactic radiofrequency gangliolysis.4. In the situation described in #3, if the patient cannot have MVD due to advanced age (older than 70) or severity of medical condition, and if the pain involves the 1st branch distribution alone or in any combination with 2nd and 3rd branches, the procedure of choice is percutaneous trigeminal balloon microcompression.5. In all situations described in #4 6. If the patient has TN with atypical features, , the most likely diagnosis is TN type 2, and the algorithm from #3–5 applies, but the patient is informed about higher chance of complications, including facial numbness and pain recurrence.7. If the patient's TN types 1 and 2  is associated with a mass lesion of the cerebellopontine angle, the surgery should address the mass lesion and the pain is expected to improve once the mass lesion is eliminated.but does not want to have any invasive intervention, the option of choice becomes stereotactic radiosurgery with Gamma Knife or, less often, linear accelerator; the patient is informed about destructive nature of radiosurgery and the lag between the treatment and onset of pain relief (1 to 6 months).8. If the patient fits description of steps #3–6 not neuralgia), and maintains some degree of sensation in the area of pain, and the pain is localized to distribution of the supraorbital or infraorbital nerves, the treatment of choice is trigeminal branch stimulation with peripheral nerve stimulation technique.9. If the patient is diagnosed with the trigeminal neuropathic pain  as a result of previous surgical deafferentation or stroke, and life expectancy more than 6 months, the treatment of choice is the contralateral motor cortex stimulation with epidural intracranial electrodes.11. If the patient has constant pain or any type of cancer-related pain in the area of face, and short (less than 6 months) life expectancy, the treatment of choice is percutaneous stereotactic trigeminal tractotomy.12. If the patient has trigeminal deafferentation pain with sensory impairment (anesthesia dolorosa), 13. If the patient's pain fits into category of other specific facial pain syndrome, such as glossopharyngeal neuralgia, cluster headaches, sudden unilateral neuralgiform pain with conjunctival injection and tearing (SUNCT), Eagle, Gradenigo, Tolosa-Hunt, Raeder, and other syndromes, a dedicated treatment modalities are considered outside of this algorithm.surgery is not recommended and the patient is managed by combination of anticonvulsants and antidepressants.14. If the patient is diagnosed with atypical facial pain, the Our algorithmic approach was used in 138 consecutive patients with medically intractable facial pain. The information about demographics, diagnoses and initial surgical interventions for these patients is summarized in Table st branch distribution. Relatively recent acquisition of Gamma Knife is reflected by its relative underutilization in our practice, but this modality is expected to be used in about 25% of all TN patients.The number of MVD and RF gangliolyses was approximately the same; RF gangliolysis was done as a repeat procedure for pain recurrence in 9 cases after previous RF ganglilolysis and in 3 cases after previous MVD. Balloon compression was used only on five occasions and only in patients with TN and pain involving 1PNS approach ,10 was uPatients with atypical facial pain (AFP) were not offered any surgical intervention, mainly on the basis of its ineffectiveness in suppressing AFP symptoms and risk of unwarranted complications. The patients understood the rationale for avoiding the surgery and proceeded with medical treatment, usually including anticonvulsant and antidepressant medications. In addition to this, several other patients with different pain conditions were advised against surgery or chose not to have operations for various reasons.From all patients followed for their facial pain, with the exception of those with AFP and those that underwent Gamma Knife SRS, 95.8% obtained pain relief upon discharge from the hospitalThe treatment algorithm for the intractable facial pain described in this paper appears to be effective for patients with a wide variety of painful conditions involving the face. It applies to vast majority of patients presenting to a neurosurgical clinic and is associated with extremely high degree of pain relief and patient satisfaction. Therefore, in our opinion, it may be recommended for use in other institutions for subsequent validation and wider adoption.AFP – atypical facial pain; ATN – atypical trigeminal neuralgia; CT – computed tomography; GPN – glossopharyngeal neuralgia; MCS – motor cortex stimulation; MRI – magnetic resonance imaging; MS – multiple sclerosis; MVD – microvascular decompression; PNS – peripheral nerve stimulation; RF – radiofrequency; SRS – stereotactic radiosurgery; SUNCT – sudden unilateral neuralgiform pain with conjunctival injection and tearing; TMJ – temporomandibular joint; TN – trigeminal neuralgia; TNP – trigeminal neuropathic pain.KVS conceived the article, treated all patients and wrote the article; HN, MEC and NM collected the data, participated in data analysis, and participated in manuscript drafting. All authors read and approved the final manuscript.


Rating scales like the visual analogue scale, VAS, and the verbal rating scale, VRS, are often used for pain assessments both in clinical work and in research, despite the lack of a gold standard. Interchangeability of recorded pain intensity captured in the two scales has been discussed earlier, but not in conjunction with taking the influence of pain etiology into consideration.In this cross-sectional study, patients with their pain classified according to its etiology  were consecutively recruited for self-assessment of their actual pain intensity using a continuous VAS, 0–100, and a discrete five-category VRS. The data were analyzed with a non-parametric statistical method, suitable for comparison of scales with different numbers of response alternatives.An overlapping of the VAS records relative the VRS categories was seen in all pain groups. Cut-off positions for the VAS records related to the VRS categories were found lower in patients with nociceptive pain relative patients suffering from chronic/idiopathic and neuropathic pain. When comparing the VAS records transformed into an equidistant five-category scale with the VRS records, systematic disagreements between the scales was shown in all groups. Furthermore, in the test-retest a low percentage of the patients agreed to the same pain level on the VAS while the opposite hold for the VRS.The pain intensity assessments on VAS and VRS are in this study, not interchangeable due to overlap of pain records between the two scales, systematic disagreements when comparing the two scales and a low percentage intra-scale agreement. Furthermore, the lower VAS cut-off positions relative the VRS labels indicate different meaning of the rated pain intensity depending on pain etiology. It is also indicated that the scales have non-linear properties and that the two scales probably have different interpretation. Our findings are in favor of using the VRS in pain intensity assessments but if still the VAS is preferred, the VAS data should be analyzed as continuous using statistical methods suitable for ordinal data. Furthermore, our findings indicate a risk to over or under estimate the patient's perceived pain when interpreting condensed VAS data. The assessment of perceived pain is necessary in the clinical setting for diagnosis and choice of treatment but also for the evaluation of treatment efficacy in a research context. The multidimensional pain sensation involves the subjective evaluations of the sensory aspect like intensity, the affective component such as unpleasantness and the cognitive aspect like thoughts related to the condition. The pain intensity, also mentioned as the severity of pain, is probably the most commonly assessed dimension of pain .The level of personal pain experience is only possible to determine indirectly by self-reported ratings often by using uni-dimensional pain rating scales that may be used for various dimensions of pain. The most commonly used scales, both in ordinary clinical work and in research, are the continuous visual analogue scale, VAS, and discrete categorical scales like the verbal rating scale, VRS, and the numerical rating scale, NRS. Although widely used, there is so far no support for a rational choice of one of these scales  even thoOn group level, the pain assessments on VAS and VRS have been variably reported as highly inter-correlated ,5 but alTo provide a rational treatment approach, classification of pain is also recommended according to its etiology ,13 or, iThe purpose of this study was to evaluate the quality of the intra-individual assessments of self-reported pain intensity on a continuous VAS (0–100) and a discrete five-category VRS, in patients with pain. The patients were separately described in groups of pain etiology. The evaluation includes inter-scale concordance, implying to which extent the assessment on one scale can be replaced by the assessment on the other, without change of the result. The consistency between the scales were also evaluated when continuous VAS assessments were transformed into discrete scales defined by equidistant cut-off positions as well as by unbiased cut-off positions relative the VRS data. The intra-individual assessment stability of both scales is evaluated by test-retest reliability. A statistical approach will be applied that is suitable for all types of data having at least an ordered structure, though distances and magnitude are unknown .Outpatients with diagnosed pain conditions were consecutively recruited from the rehabilitation medicine clinic and the spinal cord injury out patient department at the Karolinska University Hospital, in Stockholm. The assessments were conducted in accordance with the declaration of Helsinki and the patients gave their informed consent to participate. The study was approved by the Ethics Committee of Karolinska University Hospital (dnr 03–162).The patient's pains, in general located to, and/or projected to the musculoskeletal system, were previously classified according to its etiology by their physicians into – chronic/idiopathic pain, nociceptive or neuropathic pain ,13. The All patients were also asked about their prescription of analgesics and whether they had consumed any pain killing drugs on the day of assessment.This is a cross-sectional study in the sense that the three pain etiology groups will be described separately. In order to avoid assessment bias the two scales for self-rated pain intensity were administrated to the patients in random order 30 minutes prior to their appointment, scheduled in advance, with their physician. The scales were a continuous, horizontal, visual analogue scale, VAS, (0–100) with the anchor points, "no pain" and "worst possible pain " respectively and, a discrete, five-category, verbal rating scale, VRS, with the eligible alternatives – no pain (0), mild (1), moderate (2), severe (3), worst possible pain (4), see .per se, familiar to almost all patients, they were again informed about their use and encouraged to try them out prior to the real assessments. Thereafter, the patients were asked to rate their actual pain intensity by marking a level on the scales corresponding to their experienced pain intensity level. In case of not perceiving pain in rest, which was the case among some of the patients with nociceptive pain, the engaged tissue was loaded by isometric muscle contractions or by testing the respective joints active/passive range of movement in order to provoke the pain and thereby be able to rate any actual pain. The VAS was presented on paper sheets and the VRS on an electronic diary (Clinitrac®). The assessment on the electronic diary was transformed to a code-locked data base.Although the pain rating scales were, The assessment procedure was repeated for the intra-individual stability evaluation. In the analyses the pain assessments on the VAS were assigned the numeric values 0 through 100 yielding 101 ordered positions.The mean value and standard deviation (SD) were calculated for age. Frequency distributions were shown for patients' duration of pain and the use of different analgesics. The median and range (minimum to maximum) were used to describe the ordinal data of self-rated pain.The statistical method used is designed for comparing scales with different numbers of possible response alternatives ,7. As eaIn order to describe the correspondence between condensed VAS data and the VRS categories, the continuous VAS assessments were transformed to a discrete five-category scale in two ways; the cut-off positions being defined unbiased relative the VRS assessments, and being defined equidistantly, respectively.The cut-off positions of the visual analogue line, which define a discrete VAS that is unbiased to the VRS data, are constructed by pairing off the two sets of frequency distribution to each other and by identifying the cut-off positions in VAS that corresponds to the change in category of the VRS. This procedure creates pairs that are in complete order, MA = 1. Thus the condensed discrete scale based on the continuous VAS records will, under this circumstance, show a total order consistency and no systematic disagreement (be unbiased) relative the VRS. Another approach is to condense the continuous VAS records into an equidistant five-category scale that is to be compared with the five-category VRS.A high level of order consistency between scales with the same number of categories, in our case the condensed VAS and the VRS, requires a high percentage agreement  and a lack of systematic disagreement (bias) of the pairs of data. The frequency distribution of the pairs of data was evaluated by means of square (5 × 5)-contingency tables. The proportion of identical pairs defines the PA. A presence of different frequency distributions, also called marginal distributions, indicate a presence of systematic disagreement (bias), which means that the categories of the two scales have different interpretations and are, thereby, not regarded as interchangeable. Two measures of systematic disagreement were calculated; the relative position, RP, and the relative concentration, RC, with possible values ranging from -1 to 1 . The RP The stability of intra-individual assessments was calculated from test-retest pairs of data and a high level of stability requires high level of intra-individual agreement, PA, and a lack of systematic disagreement, which means zero or negligible RP and RC values.The software package of Statistica, 6.0 was used for descriptive statistics and SYSRAN 1.0 for Matlab 6 was used to calculate D, MA, RP, RC and the corresponding 95% confidence intervals for the RP and RC.Eighty patients, , recruited from the three pain groups, participated in the study and rated their actual pain intensity. All were capable to independently managing the pain assessment instruments. Analgesic drugs were most frequently prescribed to the patients in the chronic/idiopathic and neuropathic pain groups. On the day for pain intensity assessments, fewer patients had consumed analgesic drugs than what was prescribed, table The results of the first assessments were chosen for inter-scale comparison and both assessments were used for the test of intra-scale stability.The median levels of rated pain intensity on the VAS were: chronic/idiopathic pain, 59 range, 12 to 96); nociceptive pain, 25 ; neuropathic pain 64 , fig  to 96; nOverlapping VAS records relative the VRS categories mild, moderate, and severe pain were seen in all groups in this study, figures The measured level of concordance, monotonic agreement (MA), was found to be similar in all groups of etiology , revealing a difference between the ordered and disordered pairs of assessments.The cut-off positions of the discrete five-category VAS, unbiased to the VRS, were similar in the chronic/idiopathic and neuropathic pain groups  while cut-off positions in the nociceptive pain group were lower , figure The observed inconsistencies between the scales imply lack of interchangeability which were confirmed by the PA (ranging from 29% to 60%) and the measures of systematic disagreement, especially in concentration (RC), figure In the two repeated VAS assessments a low proportion of the patients, 11% to 26%, in the three groups recorded the same pain level, and 87% to 100% of the patients recorded the same level in the repeated ratings on the VRS, table The results of this study showed overlapping records between the two scales and a comparable level of inter-scale discordance in all pain etiology groups. For the VAS data condensed into a discrete scale unbiased the VRS, the cut-off positions corresponding to the labels – no pain, mild, moderate, severe and worst possible pain – were similar in patients with chronic/idiopathic and neuropathic pain but lower in the patients with nociceptive pain, indicating influence depending on pain etiology. For the equidistant discrete VAS data a systematic disagreement especially in concentration was found relative the VRS levels which means lack of interchangeability. Similar consequences of condensing continuous VAS data into discrete levels have been found elsewhere ,7 but isIn the test-retest of the two scales, a low percentage agreement were seen in assessments on VAS through all pain categories, where only 11 to 26% of the patients agreed to the same level, while a high percentage agreement were found in assessments on VRS where 87 to 100% of the patients agreed to the same level. No systematic disagreement was found in test-retest of either scale. The results of this study therefore imply that the records of self-assessed pain intensity on the VAS and the VRS, performed by the same individuals, are not interchangeable, possibly requiring different interpretation, and that the pain intensity assessments on the VAS do not have linear properties. This confirms the results of Svensson and Svensson et Berndtson  in evaluThe lack of operational definition of the VAS can possibly induce insecurity on how to relate to the continuous VAS line, thereby contributing to the low percentage agreement of the individual repeated records. The principles of pain classification, that are continuously discussed, could also contribute to the variable results of the present study. Due to its complexity, the pain classifications are not easily executed and there may be unidentified differences between the different pain etiologies, i.e. chronic/idiopathic, nociceptive and neuropathic pain. For instance, the chronic/idiopathic pain is not recommended to be regarded as a single entity  since itThere is a controversy in the literature regarding which rating scale being most sensitive to change. Because verbal scales usually have few steps, they are considered to be less sensitive than VAS. Breivik and collaborators  reportedConsistent with the findings of Ponce de Leon et al. , we founBased on the results of this study, numerals in pain rating seem meaningless since rated moderate pain intensity could be presented on the VAS with a range from 22–65 though there are suggestions of regarding ratings more than 30 mm on VAS as probable moderate and ratings more than 54 mm as probable severe when using a 4-point categorical scale .One limitation of our study could be the small number of patients and the possible presence of various pain etiologies in some individuals. Our results refer to rated, individual actual pain intensity of patients suffering from pain of different etiologies and cannot be generalized to other situations.The records of actual pain intensity on the VAS and the VRS are, in this study, not interchangeable in any of the pain etiology groups due to overlap of pain records between the two scales, systematic disagreements when comparing the two scales and a low percentage intra-scale agreement. Furthermore, the lower VAS cut-off positions relative the VRS labels indicate different meaning of the rated pain intensity depending on pain etiology. The results also indicate that the scales have non-linear properties and that the two scales probably have different interpretation. Our findings are in favor of using the VRS in pain intensity assessments but if still the VAS is preferred, the VAS data should be analyzed as continuous using statistical methods suitable for ordinal data. Furthermore, our findings indicate a risk to over or under estimate the patient's perceived pain when interpreting condensed VAS data.The author(s) declare that they have no competing interests.IL, TL, JK, CNB and LS designed the study. CNB and LS collected the data. IL extracted and analyzed the data. JK designed and supplied the electronic diaries. IL wrote the manuscript and TL and ES critically revised different sections of the manuscript. All authors contributed to commenting on drafts of the manuscript and have read and approved the final manuscript.The pre-publication history for this paper can be accessed here:Supplementary Figure 1a-b. The two rating scales used for self-assessed actual pain intensity. In the analysis, the VAS and the VRS assessments were assigned the numeric values 0 through 100 and 0 through 4 respectively, each with the anchor points "no pain" and "worst possible pain" respectively.Click here for file


Thoracotomy is associated with severe pain that may persist for years. Acupuncture is a complementary therapy with a proven role in pain control. A randomized trial showed that acupuncture was effective in controlling pain after abdominal surgery, but the efficacy of this technique for the treatment of thoracotomy pain has not been established. We developed a novel technique for convenient application of acupuncture to patients undergoing thoracotomy, and in a Phase II trial evaluated the safety of this intervention and the feasibility of doing a randomized trial.Adult patients scheduled for unilateral thoracotomy with preoperative epidural catheter placement received acupuncture immediately prior to surgery. Eighteen semi-permanent intradermal needles were inserted on either side of the spine, and four were inserted in the legs and auricles. Needles were removed after four weeks. Using a numerical rating scale, pain was measured on the first five postoperative days. After discharge, pain was assessed using the Brief Pain Inventory at 7, 30, 60 and 90 days.Thirty-six patients were treated with acupuncture. Of these, 25, 23, and 22 patients provided data at 30, 60, and 90 days, respectively. The intervention was well tolerated by patients with only one minor and transient adverse event of skin ulceration.The rate of data completion met our predefined criterion for determining a randomized trial to be feasible . This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial. Thoracotomy is a common procedure employed for primary lung cancer, with almost 30,000 performed annually in the United States . The procedure is extensive and can be associated with severe pain in patients already compromised by numerous other co-morbidities such as chronic obstructive pulmonary disease. Pain that limits respiratory function can have devastating consequences on post-operative recovery; consequently, extensive measures such as epidural catheters, local anesthetic infiltration and nonsteroidal-anti-inflammatory drugs (NSAIDs), are used to maximize analgesia and minimize side effects. ,2. AcupuThe study was approved by the Institutional Review Board (IRB) at Memorial Sloan-Kettering Cancer Center in accordance with an assurance filed with and approved by the Department of Health and Human Services. Written informed consent was obtained from each participant.We recruited adult patients at Memorial Sloan-Kettering Cancer Center who were scheduled to receive a unilateral, posterolateral thoracotomy with analgesia using an epidural catheter.Patients excluded from the study were those scheduled to undergo "hemiclamshell" or "clamshell" thoracotomy, extrapleural pneumonectomy, or esophagectomy. Patients who had received acupuncture within the previous six weeks, or who had heart valve dysfunction  were excluded. Patients with a coagulopathy precluding insertion of an epidural catheter were also ineligible. All of the patients entered on this study were operated on by a single surgeon (VR), which allowed for uniformity of surgical technique and perioperative care.Epidural catheters were placed in all patients in a pre-operative holding area with all patients in the sitting position. An iodine antiseptic was used to sterilize both the field for epidural placement and acupuncture placement. An 18 gauge Tuohy needle was used identify the epidural space, typically at the level of T6–T12. After placement of the epidural catheter, a test dose of lidocaine 1.5% and epinephrine 1:200,000 in a volume of 2–3 ml was used to identify accidental intrathecal or intravascular replacement. If either occurred, the epidural catheter was either replaced or the procedure aborted at the discretion of the physician.Eighteen semi-permanent intradermal acupuncture needles were inserted at points "BL12" to "BL19" and extra point Wei Guan Xia Shu. These points are approximately 2.5 cm lateral to the lower border of spinous process of the T2 – 10 vertebrae immediately after placement of the epidural catheter . In addition, epidural analgesia was initiated in the operating room using a continuous infusion of fentanyl (10 mcg/cc) and bupivacaine (0.05%) at a fixed rate of 4 milliliters per hour. Hydromorphone or morphine were chosen for the epidural instead of fentanyl if an adverse reaction precluded the use of the latter. Of the evaluable patients, ten were initiated on fentanyl and fifteen patients on hydromorphone. In addition analgesia was supplemented with intravenous narcotics as needed. Unless contraindicated, all patients received ketorolac 15–30 mg intravenously prior to closure and in the post-operative period as needed for up to 3 days. If a patient had persistent side effects with subjective complaints of unacceptable analgesia, the epidural opioid was changed to either hydromorphone or morphine or removed entirely; nine patients received more than one drug. Persistent hypotension was ultimately treated by removal of the epidural local anesthetic.The epidural catheter and acupuncture needles were both removed after removal of the chest tube, typically 3 to 7 days post surgery. Patients were given oral medications  as needed to manage any ongoing pain. All needles were replaced after the epidural catheter was removed, typically 24 to 48 hours before discharge from the hospital. No restrictions were placed on patients' activity level or showering. Patients were asked to remove the leg and auricular needles a week after discharge. Needles on the back were removed by an acupuncturist at the first follow-up visit, usually 3 to 4 weeks postoperatively. Patients who remained in pain at this time were offered further acupuncture treatment consisting of stainless steel, 15 mm × 0.16 mm Seirin auricular needles placed bilaterally for 20–25 minutes at the "Shenmen", "brain" and "adrenal" points in the ear. In addition, up to two needles were placed at auricular points corresponding to the sites where patients were experiencing most pain . Brief manual stimulation was used immediately after insertion. Practitioners attempted to achieve "de qi", but this was assessed by needle sensation rather than questioning of the patient. Following this treatment, acupressure metal balls were applied at the same points, and patients were taught to press each point for two minutes twice a day. They were also instructed to press on the points if they experienced exacerbation of pain. The metal balls typically remained in place for 4–7 days. These were used in preference to intradermal needles for this stage of treatment, when there is no further contact with an acupuncturist, as they do not penetrate the skin and there is no risk of infection were the patient to forget to remove them.Immediately after each needle insertion, acupuncturists completed an audit sheet verifying the acupuncture points used. These records were routinely reviewed and acupuncturists were found to have followed the acupuncture point prescription. Study acupuncturists are certified by the National Certification Commission for Acupuncture and Oriental Medicine (NCCAOM) and are licensed to practice acupuncture in New York State. They have used acupuncture in clinical practice for 3 – 25 years. All were employees of the Integrative Medicine Service at Memorial Sloan-Kettering Cancer Center.We specified that we would consider the trial feasible if at least 75% of patients tolerated the intervention; if the intervention did not interfere with surgery and routine post-operative care; if at least 75% of patients provided evaluable data at the first post-operative visit; and, if reported adverse events were acceptable. We also wanted to ensure that accrual was sufficiently rapid so that, after appropriate sample size calculations, a randomized trial could be completed in less than two years.Pain in the immediate postoperative period was assessed by a 0–10 point numerical rating scale (NRS) marked "no pain" at one end and "worst pain" at the other. Patients were evaluated between 4:00 pm and 6:30 pm on the evening of their surgery, at least two hours after leaving the Operating Room. Those not leaving by 4.30 pm had their first pain evaluation on the following day. On the first postoperative day, patients were evaluated in the morning and late afternoon. The first pain evaluation assessed pain at rest, on movement and on coughing "since you woke up from your operation." Subsequent evaluations  evaluated pain at rest, on movement and with coughing since the previous evaluation.After discharge from the hospital, pain was assessed 1 week from removal of the epidural catheter (11–18 days after surgery) and again approximately 30, 60 and 90 days postoperatively. The 11–18 day follow-up was conducted by a research study assistant by telephone; all others were conducted when patients returned for routine post-discharge appointments. Pain was evaluated using the Brief Pain Inventory (BPI), a validated pain measurement tool that measures both the intensity of pain (sensory dimension) and interference of pain in the patient's life (reactive dimension) . PatientData were analyzed using Stata 8.2 . We chose an actual sample of 25 patients. Our stopping rule was for the trial to cease once 25 patients had provided data at the 30 day follow-up.39 patients were accrued between August 2002 and September 2003. Participant flow is shown in Figure Twenty-five patients (64%) provided evaluable pain data at the first post-operative visit. Seven patients were terminated by investigators for protocol reasons such as the epidural catheter not being used, or removed early due to inadequate analgesia. None of these terminations would occur in a randomized trial due to the "intent-to-treat" principle. Of the patients who were not withdrawn, 25 of 32 provided evaluable data, a 78% data completion rate, which meets our predefined criterion for doing a subsequent randomized trial. Three patients could not be contacted and four withdrew, of whom one expressed distrust of hospital staff, one reported no pain, one did not want to deal with needles after discharge and one withdrew without giving a reason.Table None of the remaining patients requested or required removal of the acupuncture needles before discharge. Of the 25 patients with 30-day data, there were no data on needle retention for two: one patient received follow-up care at a different institution and one was discharged before reinsertion of needles. Of the 23 remaining patients, 12 (52%) either retained 16 or more needles out of 18; 4 patients (18%) retained fewer than half the needles and were thus defined as not tolerating the intervention. If we include the patient who withdrew because of complaints about the needles, 19 out of 24 patients (79%) retained more than half the applied needles at 30 days.Treatment was very well tolerated, with no patient complaining of discomfort from the needles or the Tegaderm. Seven adverse events were reported to the IRB of which six had clearly had no relationship to acupuncture, such as gastrointestinal infection. One patient was noted to have a 1 cm diameter superficial skin ulcer at 30 day follow-up. This was under the Tegaderm but away from the acupuncture needles. The Tegaderm was removed, the ulcerated area cleaned and Bacitracin ointment applied. The ulceration healed within four days.After changing from the "Japanese" style to the Acumedic needles (see Methods), we found that application of needles in the pre-operative period was rapid, and did not interfere with routine care.Pain data for the immediate postoperative period are shown in table There are multiple possible sources of post thoracotomy pain, including the skin incision, muscle division, rib fracture or resection, costochondral dislocation, neuroma formation and, less commonly, infection or tumor recurrence. Acute pain in post-operative period may lead to chronic pain characterized as "the post-thoracotomy pain syndrome." This is Absolute control of pain following thoracotomy using traditional analgesics can be associated with many side-effects, some of which (like sedation) can have devastating consequences on patients with co-morbidities such as lung disease and heart disease. Acupuncture is a well-known complementary treatment for pain  with fewRecent data suggest that acupuncture is effective in relieving pain following abdominal surgery. In thatAlthough these data are promising, we were concerned that the severity and duration of pain reported after abdominal surgery was somewhat less than is typical after thoracotomy. We felt it would be necessary to provide acupuncture stimulation over a longer period of time than attempted by Kotani et al. and hypoIn this study, we demonstrated that a novel acupuncture intervention was acceptable to staff and patients (aim 2). We found no evidence of important adverse effects (aim 4). To our knowledge, this is the first reported clinical trial to evaluate acupuncture in the management of post-thoracotomy pain. The acupuncture procedure took only five minutes to complete and did not interfere with standard preoperative care (aim 1), such as placement of the epidural catheter. Although fewer patients than intended provided follow-up data, the predicted rate of data completion for the randomized trial met our predefined criterion (aim 3). We propose that the BPI pain intensity score be used as our primary endpoint as this had the lowest coefficient of variation (aim 5). We also propose 30 day follow-up as the primary endpoint (aim 5). Although we are also interested in chronic post-thoracotomy pain, this ideal has to be considered against the potential of increased patient drop-out over time. From these and others' data , pain atAccrual was relatively slow because this pilot of a novel technique accrued patients only from a single clinician, a maximum of one day each week. To determine sample size for the trial (aim 6) we used the mean BPI pain intensity score at the 30 day follow-up (2.6) and took the upper 75th centile of the standard deviation (1.63). We assumed a minimum, clinically significant difference of 25%, i.e., that BPI scores will be 25% lower in the acupuncture group compared to placebo. This gives a hypothesized score in the control group close to 3.6. This is approximately equivalent to the expected incidence of moderate or severe pain (defined as pain score = 4) being 20% in the acupuncture group and 40% in controls. With a 5% alpha and a power of 80%, 52 evaluable patients per group are required. Allowing for 25% drop-out, we anticipate accruing approximately 140 patients. The Thoracic Service at MSKCC performs an average of 550 thoracotomies annually that would meet study eligibility criteria. We would need to accrue 13% of patients to meet our target sample within two years, or 9% to meet accrual targets within three years. Both targets seem highly feasible. The randomized trial has been approved by our Institutional Review Board and has been initiated The results of this randomized trial will determine whether acupuncture plus standard continuous epidermal or intravenous analgesia is superior to standard systemic analgesia alone.The rate of data completion met our predefined criterion for determining a randomized trial to be feasible . This novel intervention is acceptable to patients undergoing thoracotomy and does not interfere with standard preoperative care. There was no evidence of important adverse events. We are now testing the hypothesis that acupuncture significantly adds to standard perioperative pain management in a randomized trial.The author(s) declare that they have no competing interests.All authors contributed to study design. AV was responsible for methodologic and statistical aspects; BC advised on clinical aspects of implementing complementary therapies; VR and RD on surgical aspects of thoracotomy and VM on clinical pain control. Data analysis was undertaken by AV. All authors contributed to data interpretation, helped revise the manuscript for important intellectual content and approved the final version.The pre-publication history for this paper can be accessed here:


The relationship of myofascial communication systems  to activity in the subcortical central nervous system can be evaluated. Understanding this relationship has important implications for symptom control in cancer patients, because it opens up new research avenues that link self-reported pain with the subjective quality of suffering. The reciprocal body–mind relationship is an important target for manipulation therapies that can reduce suffering.Some cancer patients use therapeutic massage to reduce symptoms, improve coping, and enhance quality of life. Although a meta-analysis concludes that massage can confer short-term benefits in terms of psychological wellbeing and reduction of some symptoms, additional validated randomized controlled studies are necessary to determine specific indications for various types of therapeutic massage. In addition, mechanistic studies need to be conducted to discriminate the relative contributions of the therapist and of the reciprocal relationship between body and mind in the subject. Nuclear magnetic resonance techniques can be used to capture dynamic  Therapeutic massage is increasingly used in medical treatment programs to reduce symptoms, improve coping, and enhance quality of life The largest published report on therapeutic massage is a prospective, nonrandomized, observational study of patients treated at the Memorial Sloan–Kettering Cancer Center in New York City This intriguing observational study illustrates many of the challenges in the research into therapeutic massage. The results indicated that the size of the effect for massage in cancer patients is clinically important, and the authors have since begun a randomized controlled trial.The strength of the pilot study was the systematic collection of data from a large number of patients. Its main weakness was that it lacked a randomized control group, and therefore uncertainty remains regarding whether the intervention (massage) was the only factor that led to the improvement in the patients’ symptom scores. The patients were mainly self-selected and probably believed that the intervention would be of benefit. Symptom improvement may be a consequence of conscious belief of benefit (the placebo effect) rather than the physical manipulation or touch. In addition to the manual therapy, other ambient factors such as verbal communication, background music Currently there is a dearth of randomized controlled trials of massage therapy in cancer patients. The ones that have been reported show conflicting results that may be a consequence of variation in technique and use of non-validated symptom scores A recent prospective randomized trial completed by the department of radiation oncology, CHUM Hôpital Notre-Dame, and the Canadian Touch Research Centre in Montreal Following massage, anxiety scores in the patients were significantly reduced (by 43%) as compared with pre-massage scores. In both groups, patients experienced an average 20% reduction in anxiety between the first and the last radiotherapy session, but that result did not reach statistical significance. The massage therapy was associated with an immediate significant decrease in anxiety scores before radiotherapy , but it appeared to have no major impact on situational anxiety. However, the period of intervention and assessment was quite short, and so no conclusions can be drawn regarding long-term outcomes.The most recent publication of a randomized controlled trial of massage for cancer patients is a multicentre study from four U.K. cancer centres and a hospice To be able to design appropriate randomized controlled clinical trials, a better mechanistic understanding of therapeutic massage is required. In particular, the physiologic pathways involved need to be understood, including the connection between myofascial manipulation, blood flow, and central nervous system adaptations. Prolonged intervention with massage therapy may possibly induce more permanent neuro-physiologic adaptations because of neural plasticity.Massage therapy involves the administration of combinations of specific physical manipulations applied in a systematic way, with varying intensity, direction, rate, and rhythm, to the soft tissues of the body. The therapist may work within a particular theoretical model or framework, but the application of the manipulations is usually varied to fit the subject’s health status, desired outcomes, and preferences, and the therapist’s eclectic approach.Various types of massage have evolved from various cultural traditions . The EasSwedish massage consists of continuous systematic strokes and deep kneading and stretching to loosen tight muscles and to reduce stress. The manual techniques specifically include effleurage (smooth gliding movements intended to evoke the relaxation response), petrissage , friction (penetrating pressure with fingertips to reduce muscle spasm), and tapotement (rapid striking to stimulate tissues). Myofascial release techniques are employed to stretch and relax muscles that are tense or in spasm. Chronically tense muscles restrict blood flow and may be associated with fatigue. By applying specific pressure to connective tissues or fascia, normal alignment and function can be restored and chronic pain eliminated. The technique stretches and releases the fascia to release constriction and spasm, which causes pain.Soft-tissue release is a technique that uses specific compression and precise extension, administered in a systematic manner, to release muscle spasm and scar tissue.Trigger-point therapy (myotherapy) consists of stretching the myofascial tissue through sustained specific contact with pressure points, which helps to release tension and pain. Myotherapy is the diffusion of trigger points in muscles and the retraining of muscles to relieve pain. Trigger points are usually found in tight bands of muscle, which may radiate pain to other areas of the body. For instance, relieving a tense trigger point in the back could help to ease pain in the shoulder or to reduce headaches.Neuromuscular therapy uses static pressure on specific myofascial points to relieve pain. This technique manipulates the soft tissue of the body  and is thought to balance the central nervous system.Lymphatic drainage is a very slow, light-touch, rhythmic massage that helps the body move lymph throughout the lymphatic vessels. It reduces edema and is described as removing toxins and boosting immunity.Craniosacral therapy is a treatment approach that focuses on a gentle, hands-on technique used to evaluate and enhance the function of the cranial–sacral system. This hypothetical physiologic body system comprises the membranes and cerebrospinal fluid that surround and protect the brain and spinal cord. Craniosacral treatment is said to enhance the body’s natural healing processes, improving the operation of the central nervous system, dissipating the negative effects of stress, enhancing health, and strengthening resistance to disease.Movement re-education uses slow, rhythmic movements and sustained stretches to help restore and increase the normal range of motion in a joint and surrounding structures, while assisting with muscle relaxation.Shiatsu, meaning “finger pressure,” is a Japanese massage, a form of physical manipulation of acupuncture points and meridians. The latter are thought to channel vital energy. Working on the same principle as acupuncture, practitioners apply pressure to key points known as tsubos (Chinese acupuncture points) on the surface of the body to stimulate the flow of energy, called ki (qi or chi in Chinese).ki flows in meridians beneath the skin. The practitioner works with fingers, thumbs, elbows, knees, and feet along the meridians to remove ki blockages or overactivity , to restore areas of ki depletion , and to stretch and mobilize limbs to facilitate the flow of ki. Tui na is a similar system derived from Traditional Chinese Medicine.The Acupressure is an ancient Asian healing art that uses the fingers on the surface of the skin to press key points that modulate energy flow through meridians and chakras. Manipulation of energy flow is speculated to stimulate the body’s immune system and enhance self-healing.Reflexology consists of firm pressure to specific points on the feet, hands, or ears. Reflexology is based on the principle that these regions contain links that correspond to every other part of the body.Jin-shin do is a form of acupressure that was developed in Japan by Jiro Muraim, who mapped out a healing system based on his own body’s acupressure points and their responses to energy flow. A combination of acupressure points called “safety energy locks” is held with the fingers for a minute or more.Thai massage (nuad borarn), is an ancient bodywork system designed to unblock trapped energy and to improve vitality by applying pressure along the meridian channels.Polarity therapy is a complete system developed by Randolf Stone, a chiropractor and osteopath who believed that illness or pain in the body was cured more readily in concert with awareness and relaxation. The treatments combine therapeutic bodywork, healing intent, dietary adjustments, counselling aimed at awareness, and yoga-style exercises. The term “polarity” describes the basic nature of the hypothesized “electromagnetic force field” of the body.Massage administered by a registered (or licensed) massage therapist is very safe; complications are rare Practitioners need to be aware of the following special situations with cancer patients:Coagulation disorders, complicated by bruising and internal hemorrhageLow platelet countMedications: coumadin, acetylsalicylic acid, heparinMetastases to bone, complicated by fractureOpen wounds or radiation dermatitis, complicated by pain and infectionIn these situations, avoiding massage or lightening the touch over regions of risk may prevent complications. No evidence suggests that massage therapy can spread cancer, although avoiding direct pressure over a tumour is a sensible precaution.Requirements and laws for training and licensing vary from one U.S. state to another and from one Canadian province to another. Education, experience, certification, and licensing are all important credentials. Variation in philosophy and education is typical, and some massage therapists hold the mistaken belief that cancer is a contraindication to massage.lmt (licensed massage therapist) or lmp (licensed massage practitioner) are used after the therapist’s name. In non-licensing states, a therapist should have a cmt (certified massage therapist) as the minimum qualification. The letters nctmb indicate that the therapist has voluntarily taken and passed an examination given by the National Certification Board of Therapeutic Massage and Bodywork.The Commission on Massage Therapy Accreditation in the United States considers 500 hours of training to be a minimum basic requirement. If a therapist is licensed in the United States, the initials In Canada, the “gold standard” for massage therapy education, as set out by the Canadian Massage Therapists Alliance, demands a minimum of 2200 hours. However, considerable diversity exists in the number of hours of education and in the curricula and the types of educational institutions across the country. Some educational institutions have articulation agreements with universities for degree completion in science at the baccalaureate level.mt (massage therapist) or rmt (registered massage therapist) and to qualify for third-party insurance coverage for services. In unregulated provinces and territories, well-organized professional associations impose educational standards similar to those in the regulated provinces. Membership in provincial associations may also include title designation and access to third-party insurance coverage for services.Increasingly, massage therapy education in Canada is embracing an evidence-informed, outcomes-based model for curricula. Massage therapy is currently a regulated health profession in Ontario, British Columbia, and Newfoundland and Labrador. In the regulated provinces, students must successfully complete written and practical entry-to-practice examinations based on standards of practice set by the regulatory body. Successful applicants are eligible to use the designation For massage therapists working with cancer patients, specialized education and experience is essential. Programs for advanced training in massage care of patients with cancer are integrated into undergraduate curricula in the regulated provinces in Canada, and they are also available in continuing education programs in Canada and the United States—for example, at Memorial Sloan–Kettering Cancer Center The main indications for massage in general practice are back symptoms (20%), relaxation (19%), neck symptoms (17%), mood disorders (7%), and leg symptoms (4%). Therapeutic massage can be effective in treatment programs for pain. The mechanisms for reducing pain may consist of local effects on muscle and effects on the subconscious parts of the brain that control the experience of pain and emotions.The most common current use of therapeutic massage is in back pain and sports-related injuries. In North America, back pain is reported to occur at least once in 85% of adults under the age of 50. Nearly all of these patients will experience at least one recurrence. Back pain is the second most common illness-related reason given for a missed workday and the most common cause of disability.Back pain is non-specific in 70%–90% of cases and is associated with overuse or underuse of the back The Cochrane Collaboration has reviewed therapeutic massage for non-specific low back pain The Cochrane Collaboration has also reviewed the role of therapeutic massage and aromatherapy for cancer-related symptoms Available evidence is sufficient to indicate that therapeutic massage is a useful discipline for the relief of a variety of symptoms that affect both the body and the mind. Clinical trials of better design are required to determine precise indications for massage and to ascertain whether specific techniques are more beneficial than others for particular symptoms. Mechanistic studies are required to understand the psychophysiologic effects of massage and the influence of those effects on clinical practice.Therapeutic massage improves local musculoskeletal symptoms and function and can also positively affect mood state and pain threshold. The mechanisms by which massage exerts these multiple therapeutic effects are not yet known.Manipulation of affected muscles and fascia (as in Swedish massage) induces local biochemical changes that modulate local blood flow and oxygenation in muscle. These local effects may influence neural activity at the spinal cord segmental level and could modulate the activities of subcortical nuclei that influence mood and pain perception. In addition, massage of acupuncture points away from the painful muscles, fascia, and facet joints (as in Japanese shiatsu massage) can also modulate the activities of the limbic system and subthalamic nuclei through poorly understood somatic pathways called meridians. Beneficial late effects are possible through neural plasticity and remodelling.A meta-analysis of massage therapy research has discussed the limitations of using a medical model and suggests the use of a psychotherapy perspective It is unclear whether the therapeutic benefits of massage occur primarily as a result of manipulation of muscle and ligaments, or through the brain as a result of interaction with subcortical components of the nervous system. Those components modulate autonomic functions that influence mood and the perception of pain via the limbic system and brainstem nuclei.The multiplicity of symptoms relieved suggests that subconscious mechanisms are involved in the therapeutic effects of massage mri), positron emission tomography, and single-photon emission tomography have all demonstrated the effects of acupuncture on subcortical nuclei and the limbic system Like acupuncture, some types of massage may influence pain when applied to acupuncture points that are distant from the perceived site of the pain. Unlike therapy applied to pain at the level of the corresponding segment of the spine or dermatome, stimulation of acupuncture points influences central nervous system activity through pathways called meridians, which seem to follow musculoskeletal fascia planes We hypothesize that massage alleviates pain through at least two pathways. The first pathway is direct manipulation of soft tissue and its innervations at the level of the involved dermatome. Manipulation of the muscle and fascia may induce local biochemical changes  and can modulate blood flow and oxygenation of muscle When a peripheral source of pain persists, intrinsic mechanisms that reinforce nociception influence the pain. Chronic pain may be seen as part of a central disturbance accompanied by disinhibition or sensitization of central pain modulation. For example, patients with chronic whiplash syndrome may have a generalized central hyperexcitability from a loss of tonic inhibitory input, contributing to dorsal horn hyperexcitability Transduction is the process whereby noxious afferent stimuli are converted from chemical to electrical neural messages in the spinal cord that communicate cephalad to the brainstem, thalamus, and cerebral cortex. Noxious mechanical, thermal, and chemical stimuli activate peripheral nociceptors that transmit the pain message through lightly myelinated A-delta fibres and unmyelinated C-fibres. Nociceptors are present in the outer annular fibrosis, facet capsule, posterior longitudinal ligament, associated muscles, and other structures of the spinal motion segment. Nociceptive modulation first occurs in the dorsal horn, where nociceptive afferents converge to synapse on a single dorsal root neuron. Hyperalgesia and allodynia initially develop at the injury site. However, when central sensitization occurs, the area of pain expands beyond the initial region of tissue pathology. Attachment to emotion may increase the perception of pain and could conceivably translate into exacerbation of somatic symptoms away from a painful muscle may have a similar effect on reducing muscle pain through undefined mechanisms Swedish massage may have a direct effect primarily on muscle physiology and metabolism that, in turn, may communicate with the central nervous system through the dorsal horn afferents at the particular dermatome level. In turn, spinothalamic fibres may later activate subcortical nuclei. On the other hand, by manipulating acupuncture points that lie on meridians, shiatsu massage may initially activate sub-thalamic nuclei that can reduce pain and combat other symptoms through both subcortical gating and modulation of the limbic system. Needling of acupuncture points mrs) and fmri are powerful, noninvasive, non-radioactive techniques that may be used to evaluate the biology of manual therapies nmr). Signals can be detected only from atomic nuclear species having the quantum mechanical property of spin. The 1H hydrogen atom is the most abundant of these. It provides the signal for routine mri scanning, which produces images using the contrast of water and fat. The mrs technique measures levels of particular chemical species within an acquired tissue volume. It is especially useful for evaluating the physiology of myofascial tissue.Magnetic resonance spectroscopy ,31P mrs to assess metabolic capacity, and31P chemical shift imaging to assess local metabolic demand (oxygen uptake:VO2).the combination of mri can be used to image the neural correlates of touch and pain within the subcortical nuclei of the brain. This technique allows for indirect estimation of neural activity by detecting local hemodynamic changes, which are closely related to the integrated synaptic activity of nerve cells under physiologic circumstances Blood oxygenation level–dependent (BOLD) fThe pathways and neural centres involved in processing information from low-threshold mechanoreceptors of the skin, carried by fast-conducting myelinated afferent fibres, have been extensively investigated in nonhuman primates. Various cortical regions, including the anterior parietal cortex (primary somatosensory cortex), the lateral and posterior parietal cortices, and motor-related areas responding to mechanical stimuli have been identified mri signal increases than non-noxious stimuli do. A direct comparison between the cortical correlates of touch and pain using event-related fmri showed that, besides common activations in the contralateral postcentral gyrus and parietal operculum, pain is associated with stronger involvement of the contralateral midanterior insula, anterior portion of the midcingulate cortex, and dorsolateral prefrontal cortex The forebrain pain system partly overlaps structures involved in processing non-noxious input, but painful stimuli induce higher fmri signals in other regions involved in reward and emotion circuitry, such as the nucleus accumbens–ventral striatum and the orbitofrontal cortex, has also been demonstrated The autonomic responses to acute pain exposure usually habituate rapidly; the subjective ratings of pain remain high for more extended periods of time. Thus, systems involved in the autonomic response to painful stimulation—for example the hypothalamus and the brainstem—would be expected to attenuate the response to pain during prolonged stimulation. Areas in the brainstem are involved in the initial response to noxious stimulation, which is also characterized by an increased sympathetic response.mri examination The relative role of cognitive awareness versus subcortical modulation may be deciphered by using distraction and attention methodologies during an fper se In a study that employed covariation analysis, a functional interaction was found between the orbitofrontal cortex and perigenual anterior cingulate gyrus, the periaqueductal gray matter and posterior thalamus during pain stimulation and distraction, but not during pain stimulation When evaluating the physical effect of massage, psychophysiologic techniques to discriminate between conscious attention and subconscious neurologic interaction are important. The brain networks underlying somatosensory perception are complex and highly distributed. A deeper understanding of perceptual-related and subconscious brain mechanisms therefore requires new approaches suited to investigate the spatial and temporal dynamics of activation in various brain regions and the functional interaction of those regions.mri suggests that positive and negative tactile stimuli are both represented in the orbitofrontal cortex. The brain region in or near the amygdala is activated by pleasant touch. Most studies of the amygdala have tended to concentrate on its role in negative emotions, such as fear, but other imaging studies have found amygdala activation in response to affectively positive stimuli The development and application of refined tools for evaluating functional connectivity between neural populations will provide new insights into bottom-up and top-down mechanisms in somatosensory perception nmr techniques suggest that therapeutic massage may have distributed effects that can reduce various unpleasant symptoms.Therapeutic massage may transduce mechanical signals through skin sensation, proprioception, and non-noxious muscle perception The mechanistic links between manipulation of body tissues and corresponding relief from a broad range of symptoms are not fully understood. The effects are distributed, and reciprocal interplay between the body and mind is evident. We have literally just “touched” the surface of meridian research, but the meridian system appears to be an important communication link between myofascial tissue and the nervous system. This traditional communication system appears to link biochemical, electrical, and physiologic changes in the myofascial tissue with subcortical neurologic activity and changes in cognitive experience. The implications for symptom control in cancer patients are important, opening up new research avenues that link self-reported pain with the subjective quality of suffering. The reciprocal body–mind relationship and its manipulation is an important target for therapies that can reduce suffering.nih) in Bethesda, Maryland nih clinical trials database at clinicaltrials.gov). At June 2006, seven studies investigating the effects of massage therapy in cancer patients were registered and active.The U.S. National Center for Complementary and Alternative Medicine held a conference titled The Biology of Manual Therapies during June 9–10, 2005, at the National Institutes of Health  and validated outcome scales are essential.In addition to the manual therapy itself, ambient factors such as environment, music, and aroma can influence outcome. The objectivity of research is complicated by the relationship and transference between therapist and client. The possibility exists that benefits may come about more from factors such as the recipient’s attitude toward massage therapy, the therapist’s personal characteristics and expectations, and the interpersonal contact and communication that take place during treatment than from the specific form of massage therapy used or the site to which it is applied.Only a combination of mechanistic research and well-designed clinical trials will clarify the reciprocal relationship between body and mind and will determine the utility of manual therapies for symptom control in cancer patients.