The Functional Index for Hand Osteoarthritis (FIHOA) is a simple tool to assess functional impairment for hand OA patients. The purpose of this study was to translate the FIHOA into the Thai language, and validate it in Thai hand OA patients.The FIHOA was translated into Thai (T-FIHOA) according to the principles of cross-cultural adaptation and administered to 102 hand OA patients recruited between September 2020 and July 2021 together with the modified Health Assessment Questionnaire (mHAQ), Disabilities of the Arm, Shoulder and Hand (DASH), and visual analogue scale (VAS) for hand pain. Spearman’s correlation coefficient and intraclass correlation coefficient (ICC) were used to check the test-retest reliability of each item and the total scores in the translated questionnaire. The internal consistency reliability was evaluated using Cronbach’s alpha. The external construct validity was assessed using correlations between the T-FIHOA, mHAQ, DASH and hand pain VAS.P <  0.01) and moderate to strong correlations with the mHAQ , and DASH score . The T-FIHOA had the highest effect size (ES) and standardized response mean (SRM) (− 0.37 and − 0.58 respectively) among all questionnaires except for the VAS when assessing changes between baseline and week 4.The T-FIHOA had a unidimensional structure. The ICC was > 0.9 and the Cronbach’s alpha of 0.92 indicated excellent reliability and internal consistency, respectively. The external validity tests indicated moderate correlation with the hand pain VAS (r = 0.37, The T-FIHOA is a good and reliable assessment tool freely available for practitioners/researchers to evaluate functional impairment in Thai hand OA patients. Osteoarthritis (OA) is characterized by joint pain, often associated with use, and impaired joint function. Osteoarthritis can affect any joint, most commonly the hand, knee, spine, and hip. In the hand, the distal interphalangeal joint, proximal interphalangeal joint, and first carpometacarpal joint are the most commonly affected . In the A number of instruments have been developed to measure pain and functional disability in patients presenting with possible OA, ranging from physical assessment by a trained assessor to self-administered hand disability questionnaires. The Arthritis Impact Measurement Scales 2 (AIMS2) , the FunFIHOA.net. Currently, the FIHOA questionnaire is one of the most popular for assessing physical function in patients with OA of the hand . The OstAlthough there are Asian versions available as mentioned, neither the Korean  nor the The translation process followed the international guidelines as described by Beaton et al.  This metAn expert committee was initiated including two persons whose Thai was the mother language and who were also fluent in English. Translator 1 was an orthopedist who was familiar with the concepts being examined in the questionnaire. Translator 2 was a staff member of the Liberal Arts Faculty, without any medical or clinical background. Both translators independently translated the questionnaire into Thai. The two versions were assessed by the expert committee and synthesized into a preliminary version of the T-FIHOA. It was then back translated into English independently by two English native professional translators, one with a medical background and one without from the faculty of Liberal Arts, both of whom were blinded to the study aims and FIHOA concepts. After back translations, there still was remaining linguistic and culture problems. In Thai culture, Thai people did not handshake with others. People have to pay respect to the elders or the activities such as prostate together after the chant. To adapt this item in order to keep capturing the activities and function assessed, these problems were resolved through consultation with the developers of the FIHOA (E.M.) by discussion. The T-FIHOA was pretested on 15 Thai hand OA patients to identify potentially difficult words or phrases and a written report submitted to the developers. The final translation of T-FIHOA including cultural adaptation was finalized (Table Hand OA patients were recruited at the outpatient Orthopedics department of a single tertiary center in the South of Thailand September 2020 and July 2021. The classification used for the diagnosis of hand OA was the American College of Rheumatology (ACR) classification criteria . The stuData collected on the date of enrollment were medical history including hand OA history, duration of hand pain/stiffness, and prior and current treatments. Postero-anterior plain radiographs were obtained to assessing hand OA severity. Patient’s scoring of the T-FIHOA, the Thai version of the modified - Stanford Health Assessment Questionnaire (mHAQ), the visual analogue scale for pain (VAS pain), and the Thai version of the Disabilities of the Arm, Shoulder and Hand (DASH) were collected. We assessed the test-retest reliability at one to 2 weeks’ time-interval using T-FIHOA in patients whose symptoms and treatment remained stable. To perform the retests, the investigator could use different means including a face-to-face visit or a telephone interview depending upon the convenience for participants. In order to measure the responsiveness, the T-FIHOA and DASH questionnaires were assessed at baseline and 6 weeks. Treatment for hand osteoarthritis started after collecting baseline data. Patients received systemic pharmacological treatments as well as education for joint protection and strengthening exercises. If the symptoms were not improved, treatment and dosages could be adapted.The FIHOA is a 10-item self-administered. The answers are scored according to a 4-point scale, as follow: 0, possible without difficulty; 1, possible with slight difficulty; 2, possible with important difficulty; 3, impossible. The total score ranges from 0 to 30 . In thisDASH, Thai version , is madeParticipants were asked to score the level of pain intensity on a horizontal scale from “0 = no pain” to “100 = worst pain imaginable.”Thai HAQ includes 20 items in eight domains adapted from the original HAQ-DI to suit Thai culture and activities . The abit test was used to compare demographic and clinical characteristics of the patients between the symptomatic and non- or mildly symptomatic hand OA groups. To compare the scores of the T-FIHOA between test and retest, the Wilcoxon’s signed-rank test was used. To assess the validity and reliability of the T-FIHOA we used the Spearman’s correlation coefficient (Spearman’s rho), the intra-class correlation coefficient (ICC), the weighted Kappa, and the Cronbach’s alpha. The internal consistency was assessed by using a factor analysis. All analyses were performed using the R program Version 3.4.5 . For comparisons, a P value of < 0.05 was considered significant.Demographic data of the study population were presented as mean ± standard deviation (SD) for continuous variables and frequency with percentage (%) for categorical variables. The independent Student Spearman’s rho, ICC, and weighted Kappa were used to evaluate the test-retest reliability. ICCs were calculated for the total scores. The two-way mixed single measures test was used for estimating the reliability of each item individually. The Spearman’s rho values range from 0.1–1.0 and are considered as weak (0.1–0.3), moderate (0.31–0.5), or strong (> 0.5) respectively. An ICC ≥0.7 indicates a good reliability at the scale level.The internal consistency  was assessed by calculating Cronbach’s alpha. If the value was > 0.7 the internal consistency was considered acceptable to good.Factor analysis was used to evaluate the internal construct validity while external validity was examined by assessing the correlations between the T-FIHOA and the Thai version of the mHAQ, and the pain VAS using Spearman’s correlation coefficient.One hundred and two patients answered the T-FIHOA. All patients completed the questionnaires. The demographic characteristics of the participants are presented in Table P <  0.01). The mean mHAQ score was also higher in the symptomatic hand OA group (1 ± 0.8) than in the non/mildly symptomatic group . There were no statistically significant differences between the two groups with regard to demographic or baseline clinical characteristics, including age , disease duration , proportion of women (40 (78.4%) vs 38 (76.5%), P = 0.82), body mass index , and DASH score  except for the number of radiologically affected joints . and pain score  which were higher in the symptomatic group.The mean T-FIHOA score was obviously higher in the symptomatic hand OA group than in the non/mildly symptomatic group . Spearman’s rho value was 0.99 for the T-FIHOA total score; Spearman’s rho ranged between 0.87 and 0.99 for each item and for the global score. ICC were excellent both for the total score (ICC = 0.99), and for each single item .The patients completed the T-FIHOA twice at a 7–14 days intervals. Treatments between two assessments remained stable. Table P <  0.01), as shown in Table Internal consistency was excellent with a Cronbach alpha value of 0.93. When deleting 1 item after another, Cronbach’values remained high, ranging from 0.92 to 0.93.Each individual items of the T-FIHOA was strongly correlated to the total score. All correlations were statistically significant (P <  0.01). The eigenvalue of the first factor was 6.37, explaining 42% of the global variance of the T-FIHOA, whilst, the second factor accounted for 24% of the variance. The scree plot had a single elbow curve  of 441.26 (P < 0.01) which was expected since the FIHOA is not a pain scale, and strong significant direct correlations between T-FIHOA and mHAQ  and T-FIHOA and the DASH score   were included in the responsiveness analysis. Change in scores before the treatment and 4-week follow up were compared using the Wilcoxon signed-rank test. The effect size (ES) and standardized response mean (SRM) were calculated. ES was defined as mean change divided by the standard deviation (SD) and SRM was defined as mean changes divided by the SD of that change. The responsiveness was evaluated by comparing of ES and SRM between the T-FIHOA and other measurements. Results are shown in Table Symptomatic participants defined by a total T-FIHOA score ≥ 5  –24, 27. Our study has some limitations. First, our population was only recruited from a tertiary care unit in the South of Thailand which may not reflect data in the overall Thai population. However, due to the simplicity of items and the socio-cultural similarity between Thai areas, we believe that our results are valid and of use for the entire Thai population. Second, this study examined the T-FIHOA only with educated patients because illiterate people would be unable to read the Thai alphabet and, particularly could not respond to item 9 which asks “Can you write for a long period of time?”The T-FIHOA showed good psychometric properties to assess hand OA-related functional disability in Thai people. Since it is now validated, and freely available for the community, it may and should be used by all practioners in daily practice hand OA, assessment, and by researchers in clinical trials or surveys.


Chronic pain is associated with an elevated risk of suicidal ideation (SI).We aimed to examine if the presence or the search for Meaning in Life (MiL) are associated with less SI and explore whether MiL profiles emerge in our cohort. These profiles can be described as high presence–high search, high presence–low search, low presence–low search, and low presence–high search.In this observational study, we recruited 70 patients who were referred to the Multidisciplinary Pain Center of the Geneva University Hospitals and who answered positively to question 9 on the Beck Depression Inventory, 2nd Edition, investigating SI. Patients who agreed to participate in the study were further investigated; they participated in a structured diagnostic interview to screen for psychiatric diagnoses. During this interview, they completed the Meaning in Life Questionnaire and the semistructured Scale for Suicide Ideation (SSI) to assess the characteristics and severity of SI.R=–.667; P<.001). The results also showed a negative and statistically highly significant correlation between the score of the search for MiL and the SSI . The results thus pointed to the presence of MiL as a potential protective factor against the severity of SI, while the search for MiL is also a possible resiliency factor, although to a lesser extent. The profile low presence–low search grouped the vast majority (47%) of the patients; in these patients, the mean SSI score was 14.36 (SD 5.86), much higher compared with that of the other subgroups.There was a statistically significant correlation between the presence of MiL subscale and the SSI. These 2 scales had a negative and statistically highly significant correlation (This study’s results point to MiL as a concept of interest regarding devising psychotherapeutic interventions for chronic pain patients in order to reduce the suicidal risk and more accurately determine patients’ suffering. Patients suffering from chronic pain conditions are at an elevated risk of suicidal behavior (SB). The literature points to a 20% to 40% prevalence rate of suicidal ideation (SI); lifetime prevalence of suicidal attempts (SA) is estimated between 5% and 14%; further, the risk of completed suicide is doubled in patients with chronic pain as compared to controls . NumerouHowever, the literature also highlights the need for further exploration of other possible risk and protection factors to improve the characterization of the SB risk profile in these patients . Using tAccording to the conceptualization of MiL, this construct is a web of connections that help to read and understand the pain experience and create strategies directed at achieving the expected outcomes regarding reducing pain and its consequences . This moDrawing on these studies and the MiL construct, this study aimed to investigate the relationship between MiL and intensity of SI in patients with chronic pain presenting SI.Our objectives were as follows:Examine whether the presence of or search for MiL are associated with less SIExplore whether previously described MiL profiles  emerge in our cohortThis study’s results will permit future exploration into further psychotherapeutic interventions integrating MiL profiles on the model of already existent standards for patients with other somatic conditions -29.The Division of Clinical Pharmacology and Toxicology and the Service of Liaison Psychiatry and Crisis Intervention at the Multidisciplinary Pain Center (MPC) of the Geneva University Hospitals conducted this observational study . The MPCDiagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). During this same interview, patients completed the Meaning in Life Questionnaire (MiLQ) ) that was lower than the average score of the whole group (20.13). In contrast, in patients with a lower score on the SSI (SSI<6), the correlation between the presence of MiL and SI was negative but not significant and the mean score on the MiL presence subscale, considerably higher, was 29.50 (SD 5.44), above the mean score for the whole group.Considering the results of the MiLQ in the 2 subgroups  highlighted the following results: in the first subgroup (SSI ≥6), the negative correlation between the severity of SI and the presence of MiL was statistically very significant . In the subgroup of patients with a weaker SI (SSI<6), the mean score for the search for MiL was 21.17 (SD 7.17), higher than the mean score of the whole group (18.14). However, in this subgroup, the correlation between the search for MiL and SI was not significant.The results were more contrasted for the search for MiL in these 2 subgroups. In the subgroup of patients with higher SI (SSI≥6), the mean score for the search for MiL was 17.52 (SD 8.84), close to the mean score of the whole group (18.14). In this subgroup, there was a strong and significant negative correlation between the search for MiL and SI  and those with lower SI (SSI<6), with We examined the relationship of the different profiles of MiL with SI, using the grouping Dezutter et al  describeThis study showed that MiL is associated with SI in patients with chronic pain. Our results showed that the presence of MiL seemed to be a potentially protective factor against SI. The statistically significant negative association between the subscale presence of MiL and SSI, with the presence of MiL actually associated with a decrease in the severity of SI, further supports our results. We found this negative correlation both in the patients with a high SI (SSI ≥6) and in those who presented a lower SI (SSI <6). These results are in line with those of the literature, which highlight this negative correlation between the presence of MiL and SI among students , militarThe results are less straightforward regarding the search for MiL. In our sample, we found a negative and significant correlation between the search for MiL and SI. This means that the patients who seek MiL, regardless of the presence of MiL, have less intense SI as compared to those who do not. Furthermore, this significant negative correlation is also found in the subgroup of patients who present with high SI (SSI ≥6), but this association is not significant in patients with less intense SI (SSI <6).Contrary to the results for the presence of MiL, the difference in the scores on the search for MiL subscale is not significant between patients with strong SI (SSI ≥6) and patients with less intense SI (SSI <6). This shows that while the presence of MiL is clearly higher in patients with lower SI, the search for MiL tends not to be significantly different between patients with high versus low SI. Previous studies have also found a protective effect of searching for MiL against SI , but othIn our group, neither presence of nor search for MiL were associated with sociodemographic or pain-related characteristics, except for professional activity, which was associated with the presence of MiL. This is also in line with previous research suggesting that patients who present MiL display a higher level of adaptation, including in the professional field . Fewer wFour profiles of MiL  have been described in chronic pain patients . The patThe literature has reported that when the search for MiL is high and associated with a high presence of MiL, the determining effect of the search for meaning appears to decrease . TherefoHowever, the search for MiL when no meaning is presently identified is associated with higher SI scores, thus pointing to the search for meaning as more anxiety provoking and stressful. Some have suggested that such a pattern might result in an adaption that is more problematic and less optimal psychological well-being . In our Finally, our data confirmed that the presence of and the search for MiL are positively and significantly correlated, which suggests that the 2 constructs may depend on one another. This is not in line with previous research ,24,47, bOur study has limitations that need acknowledgment. First, the study sample is small, and thus not allowing for the construction of subgroups using the participants’ sociodemographic and clinical characteristics; however, the sample allowed investigating and categorizing the patients according to the MiL and SI dimensions. Second, the MiLQ has not been extensively validated in French; however, it has been used in various contexts, particularly psychiatric emergencies, in its current version . Third, Taken together, our results regarding the different MiL profiles and associated risk factors highlight the place to be given to individual participants. Indeed, MiL profiles may allow clinicians to consider mental and somatic suffering; however, the search for the coherence of a constellation  should not mask the specific form of the individual patient’s suffering. Using MiL profiles can help clinicians recognize their patient’s suffering while keeping in mind the necessity to consider the patient’s singularity even while using validated tools to describe mental states and organization. In chronic pain patients, the continuity and attention of clinicians to maintain the associative work of the patient’s discourse is of main concern; indeed, facing suicidal crisis, the process at work in the patients can hinder this work. Considering the concept of MiL should support clinical work aimed at providing the most adequate response to patient suffering, as it has proven possible in the context of psychiatric emergencies ,62. PsycOur study supports a probable protective role of MiL against the severity of SI in patients with chronic pain presenting with SI. Further studies should be conducted to better enlighten the complex relationship between suicidal risk, prevention, and intervention strategies in chronic pain patients to provide new perspectives. The results stress the importance of thorough patient interviews regarding bringing theoretical conceptualizations into daily clinical practice.


Hip or knee osteoarthritis (OA) is one of the main causes of disability worldwide and occurs mostly in the older adults. Total hip or knee arthroplasty is the most effective method to treat OA. However, severe postsurgical pain leading to a poor prognosis. So, investigating the population genetics and genes related to severe chronic pain in older adult patients after lower extremity arthroplasty is helpful to improve the quality of treatment.We collected blood samples from elderly patients who underwent lower extremity arthroplasty from September 2020 to February 2021 at the Drum Tower Hospital Affiliated to Nanjing University Medical School. The enrolled patients provided measures of pain intensity using the numerical rating scale on the 90th day after surgery. Patients were divided into the case group (Group A) and the control group (Group B) including 10 patients respectively by the numerical rating scale. DNA was isolated from the blood samples of the two groups for whole-exome sequencing.P < 0.05), including CASP5, RASGEF1A, CYP4B1, etc. These genes are mainly involved in biological processes, including cell–cell adhesion, ECM–receptor interaction, metabolism, secretion of bioactive substances, ion binding and transport, regulation of DNA methylation, and chromatin assembly.In total, 661 variants were identified in the 507 gene regions that were significantly different between both groups (The current study shows some variants within genes are significantly associated with severe postsurgical chronic pain in older adult patients after lower extremity arthroplasty, indicating a genetic predisposition for chronic postsurgical pain. The study was registered according to ICMJE guidelines. The trial registration number is ChiCTR2000031655 and registration date is April 6th, 2020.The online version contains supplementary material available at 10.1186/s13018-023-03683-y. Hip or knee osteoarthritis (OA) is one of the main causes of disability worldwide and occurs mostly in the older adults. With an aging global population and the increase in the incidence of obesity, the incidence of OA is expected to further increase . Total hPrevious studies have shown that the development of chronic pain has complex genetic characteristics . To explChronic pain after general hip or knee arthroplasty is a difficult postsurgical complication that affects patients' surgical satisfaction, recovery, and quality of life. When patients with medium to severe pain cannot relieve their pain their physical and mental health and daily life are severely and negatively impacted. The variation in pain between patients suggests that a genetic component is involved. However, to date few studies have been conducted on the relationship between lower arthroplasty and CPSP. Therefore, the current study sequenced whole genome exon variants of older adult patients with severe chronic pain after lower extremity arthroplasty. The susceptibility genes related to CPSP were investigated to provide a direction for the development of new clinical treatment methods and identify potential susceptibility biomarkers for patients with chronic postoperative pain.Elderly patients who underwent lower extremity arthroplasty in Drum Tower Hospital Affiliated to Nanjing University Medical School from September 2020 to March 2021 were selected and followed up for postoperative pain assessment using the numerical rating scale NRS. The elderly osteoarthritis patients selected were all caused by joint degeneration rather than fractures or necrosis caused by other reasons. They were performed operations by the same group of doctors and operation method. All patients signed informed consent and were authorized by the ethics committee of Drum Tower Hospital Affiliated to Nanjing University Medical School . Inclusion criteria: (1) Age ≥ 65 years old; (2) American Society of Anesthesiologists (ASA) classification II–III; (3) Patients undergoing lower extremity arthroplasty; (4) Operation duration ≥ 60 min; (5) Patients recorded in electronic medical record system; (6) Patients agreed to participate in the study and signed the informed consent. Exclusion criteria: (1) With gene deficiency disease; (2) Having history of opioid abuse; (3) Using drugs that induce or inhibit liver isoenzymes  in 4 weeks before operation; (4) Combined with peripheral neuropathy and psychiatric history, chronic pain and long-term opioid use history; (5) With poor body conditions affecting the perioperative pain evaluation; (6) Patients can’t cooperate and communicate with.The patient's NRS score being ≥ 4 on the 90th day after operation was identified as having severe CPSP. A total of 10 patients were judged to have severe CPSP (group A). 10 patients hospitalized in the same period without chronic postsurgical pain (NRS score = 0 on the 90th day after operation) were randomly selected as the control group (group B).5 ml peripheral blood of the patients was collected from the artery, then the DNA was extracted using the Magnetic Universal Genomic DNA Kit . The degree of DNA degradation and the presence of RNA and protein contamination were analyzed by agarose gel electrophoresis. We used Qubit 3.0 (Life Technologies) to accurately quantify DNA concentration. DNA samples containing more than 0.6 μg were used to build the database.Full exon sequencing (WES 1000 g) was performed by Agilent's liquid chip capture system. Genomic DNA extracted from peripheral blood for each sample was fragmented to an average size of 180–280 bp and subjected to DNA library creation using established Illumina paired-end protocols. The Agilent SureSelect Human All ExonV6 Kit  was used for exome capture according to the manufacturer’s instructions. The Illumina Novaseq 6000 platform  was utilized for genomic DNA sequencing in Genechem Bioinformatics Technology Co., Ltd  to generate 150-bp paired-end reads with a minimum coverage of 10 × for ~ 99% of the genome (mean coverage of 100 ×). After sequencing, base call files conversion and demultiplexing were performed with bcl2fastq software (Illumina). The resulting fastq data were submitted to in-house quality control software for removing low quality reads, and then were aligned to the reference human genome (hs37d5) using the Burrows-Wheeler Aligner (bwa), and duplicate reads were marked using Sambamba tools. ANNOVAR software was used to annotate the variants.Filtering of rare variants was performed as follows: (1) variants with a MAF less than 0.01 in 1000 genomic data , esp6500siv2_all, gnomAD data (gnomAD_ALL and gnomAD_EAS) and in house Genechem-Zhonghua exome database from Genechem; (2) Only SNVs occurring in exons or splice sites (splicing junction 10 bp) are further analyzed since we are interested in amino acid changes. (3) Then synonymous SNVs which are not relevant to the amino acid alternation predicted by dbscSNV are discarded; The small fragment non-frameshift (< 10 bp) indel in the repeat region defined by RepeatMasker are discarded. (4) Variations are screened according to scores of SIFT, Polyphen, MutationTaster and CADD software. The potentially deleterious variations are reserved if the score of more than half of these four software support harmfulness of variations. Sites (> 2 bp) did not affect alternative splicing were removed.t-test or Mann Whitney U test was used to compare continuous data of the two groups , and categorical data of the two groups  was compared using chi-squared test or Fisher test. Binary logistic regression analysis was used to evaluate the correlation between each variant loci and the risk of chronic pain in patients after lower extremity arthroplasty. Level of P values less than 0.05 (two-sided) was regarded as statistically significant in all tests. The FDR correction method was used to test multiple hypotheses on the data, but the sample size was small, so the corrected P value had no reference significance. The cluster profiler package of R language was used for gene ontology (go) enrichment analysis and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The significantly different target genes were selected for annotation (P < 0.05), to get the terms and pathways of relevant genes enriched in.SPSS 22.0 and R software were used for statistical analysis. Normal distribution of continuous data was assessed, which conformed to normal distribution was expressed as mean ± standard deviation (As shown in Table P < 0.05). Synonymous variants and variants in introns and intergenic regions were removed from further analysis as they typically have little impact on function. Thereafter, 661 variants in 507 genes with potential functional impacts remained [After filtering all loci for quality control, the correlation between 339,767 variants and severe chronic pain in patients after lower extremity arthroplasty was analyzed using binary logistic regression  enrichment. Considering a significance threshold cutoff of In the current study, we identified 661 variants in 507 genes associated with CPSP. These results were obtained after bioinformatics analysis and require further functional validation. These genes are associated with numerous functions; however, many are related to neuroinflammation, cognitive function, nervous system development, and key metabolic enzymatic activities.CASP5), which encodes for a proinflammatory caspase related to inflammasome formation, was significantly associated with CPSP. Recently, Islam et al. found that blood CASP5 levels were markedly increased in patients with neuropathic pain, suggesting that inflammation is involved in the occurrence and development of neuropathic pain [CASP5 variants in the patients with severe CPSP was significantly higher than that in the control group. According to other studies, the upregulation of CASP5 can promote the progress of OA and increase the sensory input to the central nervous system, thus aggravating pain [CASP5 variants in patients with OA may lead to increased CASP5 expression levels after arthroplasty, which subsequently increases the risk of severe CPSP. CASP1 of the caspase family was also significantly related to CPSP in our study. Some studies have shown that NLRP3-CASP1 mediates the promotion of microglia in neuroinflammation. However, whether it regulates the occurrence or development of pain remains to be further verified [Caspase 5 gene , which is widely expressed in the nervous system, was also significantly associated with CPSP. ASIC1 is a proton-gated cation channel that is activated by extracellular acidification. It has been reported that MiR-485-5p is involved in the development of OA and that reducing the expression of MiR-485-5p can cause inflammatory pain by upregulating ASIC1expression. Therefore, MiR-485-5p/ASIC1 may be a potential target for the treatment of inflammatory pain in patients with OA [ASIC1 is also expressed in microglia. In inflammation, ASIC1 promotes microglia migration and releases inflammatory cytokines, such as NOS and COX-2; this indicates that ASIC1 is involved in neuroinflammatory response [ASIC1 variant was observed in the control group. It can be speculated that this variant interferes with the correct transformation of ASIC1 into a protein with normal physiological function, thus reducing the risk of CPSP in the control group. The above hypothesis can be evaluated through further functional verification. These findings suggest that blocking ASIC1 may be a powerful method for the prevention and treatment of chronic pain after lower extremity arthroplasty.Acid-sensitive ion channel 1 gene , is expressed in T cells in the brain. As a costimulatory molecule for T-helper 1 cell activation, ADAM12 mediates tissue inflammation and may play a role in the formation and development of pain. The polymorphism of ADAM12 has also been significantly associated with knee OA [BCAP29, IDO2, IGFBP1, TLR10, and TNC. How these genes regulate and affect chronic pain after arthroplasty requires further exploration [Another significantly associated gene, A disintegrin and metalloproteinase 12  and is expressed in the spinal cord. A study demonstrated that peripheral inflammation significantly increases the level of eLOX3 in the spinal cord and the metabolites of eLOX3. These metabolites promote inflammatory pain via inflammatory cytokines [ytokines .PLCE1 encodes phospholipase C ϵ-1, which can stimulate the expression of many inflammatory cytokines, including TNF-α, IL-4, and IFN-γ. It can also activate the NF-κB signaling pathway to promote inflammation and may play an important role in inflammatory pain [ory pain . The aboMZF1 encodes for a myeloid zinc-finger transcription factor that regulates the transcription process of related proteins. Many studies have shown that MZF1 plays an important role in neuropathic pain. MZF1 can regulate the expression of voltage-gated K+ channel and TRPV1 genes, thus enhancing the excitability of dorsal root ganglion (DRG) neurons, thereby strengthening the transmission of pain signals and promoting the development of neuropathic pain [ZNF382 encodes for zinc-finger protein 382, which is a transcription factor highly expressed in the nervous system. ZNF382 is persistently downregulated in injured DRG neurons, losing its binding to the silencer upstream of the Cxcl13 promoter, which promotes the transcription of Cxcl13. This eventually contributes to the development and maintenance of neuropathic pain [CPSP is usually multifactorial and is associated with not only postoperative inflammation but also neuropathic factors, such as peripheral nerve injury, and pain regulation disorder in the central nervous system during operation . AKAP12/hic pain , 50, 56.hic pain . These gTET1 from the current study is of particular interest. The TET enzyme encoded by TET1 is essential for brain function. TET1 participates in the regulation of DNA demethylation, gene expression, synaptic transmission, and memory formation. Its mutation is related to human cognitive dysfunction. After injury, TET1 is upregulated so that DNA demethylation at the CpG site of BDNF and mGluR5 promoters is mediated by the TET1 increase, which increases the transcription of BDNF and mGluR5 and promotes the development of abnormal neuropathic pain. TET1 also regulates the function of astrocytes through Ca2+ signaling, thus affecting neuronal development and cognitive function [Combined with the above-related factors leading to CPSP, function , 19, 52.DCC, which encodes the DCC receptor, is highly expressed in dopamine cells and interacts with Netrin-1, which plays an important role in regulating synaptic development. Its polymorphism is closely related to the susceptibility to emotional disorders, psychosis, and addiction [DCC showed a significant correlation with chronic pain in another study, further supporting the correlation between nervous system development and pain [LASP1 plays an important role in formation and maintenance of synaptic in the hippocampus in rats [LASP1 have also been associated with many neurological diseases, such as schizophrenia, autism, and bipolar disorder [AP1S1 encodes an adaptor protein complex that is related to synaptophysin and the vesicular acetylcholine transporter, which is very important for spinal cord development; Slitrk2 mediates excitatory synapse formation and transmission; and GPR50 encodes the G protein coupled receptor 50 that is associated with synaptic plasticity [CLIP3 regulates astrocyte proliferation and myelination and participates in regeneration after nerve injury [Although many of our findings are not specifically associated with pain, these genes are involved in the development of the nervous system or the repair process after injury, which is likely to play a role in neuropathic pain. For example, ddiction . Similarand pain . Similar in rats . Geneticdisorder . In patiasticity , 26, 39.e injury , 7. In pAMACR, encoding α-methylacyl-CoA racemase, catalyzes key steps in ibuprofen metabolism [AOX1 encodes xanthine dehydrogenase, which metabolizes aza- and oxo-heterocycles representing the scaffold of many drugs like morphine and fentanyl [CYP1A1 encodes cytochrome oxidase and participates in steroid catabolism [NAAA encodes for the hydrolase of PEA, and variants in NAAA may affect the level of PEA, thus affecting the activation of corresponding receptors, causing the biological transformation from acute pain to chronic pain [Polymorphisms not only affect patients’ sensitivity to pain, but also the large variation in individual efficacy of analgesic drugs. Some genes may encode for the key metabolic enzyme for these drugs. Variants in these genes alter enzyme activity, preventing drug metabolism or transformation into active forms in the body, leading to great differences in the demand for analgesic drugs in different patients. For example, tabolism , while Afentanyl  and CYP1tabolism . In addinic pain .PIP2) is located at the key convergence point of multiple receptors, ion channels, and signal pathways that promote chronic pain. Downregulating PIP2 in neurons can weaken receptor signals, which is a potential new method for the treatment of pain [PI3K and its downstream Akt are widely expressed in the spinal cord, especially in the lamina I–IV of the dorsal horn, where the primary afferent nerve fibers mostly terminate. At present, many studies have confirmed that the PI3K/Akt pathway plays a key role in the development and maintenance of chronic pain [As mentioned in the results, the enrichment analysis found many pathways, molecular functions, and biological processes associated with CPSP. The most significant findings are discussed in this study. Cell adhesion molecules mediate the migration of leukocytes to the injured tissues and the release of opioids locally (mainly opioids β-endorphins), which produce an analgesic effect, and block adhesion molecules . Other s of pain . In OA,  of pain . The sti of pain  found thCASP5, ASIC1, and ADAM12 are of particular interest as these nervous system genes are closely related to chronic pain and immunity in patients who undergo hip and knee arthroplasty. Reduction of the occurrence or degree of postoperative chronic pain by regulating these genes would greatly improve the therapeutic effect and the quality of life of older adult patients after lower extremity arthroplasty. Furthermore, the study may provide a basis and reference for further research on CPSP and gene susceptibility. Additionally, certain biomarkers can be explored and new intervention targets predicted to identify high-risk patients with CPSP.Pain after total hip or knee arthroplasty has always been of clinical concern as it greatly decreases the quality of life of the patients and increases the consumption of family and social resources. At present, clinicians mostly use multimode analgesia, combining nerve blocks and a variety of analgesic drugs to reduce pain. However, the prevalence of CPSP remains high , 32, 49.Additional file 1. S1. General table of groupAB SNP.Additional file 2. S2. IDs of SNP.Additional file 3. S3. Genotypes of each individual.Additional file 4. S4. Metascape result.


Refractory abdominal pain is a cardinal symptom of chronic pancreatitis (CP). Management strategies revolve around pain mitigation and resolution. Emerging evidence from observational studies highlights that surgery may result in superior pain relief when compared to endoscopic therapy; however, its impact on long-term quality of life or functional outcome has yet to be determined.A search through MEDLINE, PubMed and Web of Science was performed for RCTs that compared endoscopic treatment with surgery for the management of CP. The main outcome measure was the impact on pain control. Secondary outcome measures were the effect on quality of life and the incidence rate of new onset exocrine and endocrine failure. Data was pooled for analysis using either an odds ratio (OR) or mean difference (MD) with a random effects model.p = 0.0008]. No difference was noted in the incidence of new onset endocrine or exocrine failure between treatment strategies.Three RCTs were included with a total of 267 patients. Meta-analysis demonstrated that operative treatment was associated with a significantly higher rate of complete pain control (37%) when compared to endoscopic therapy (17%) [OR ) 2.79 (1.53–5.08), Surgical management of CP results in a greater extent of complete pain relief during long-term follow-up. Further research is required to evaluate the impact of the time interval between diagnosis and intervention on exocrine function, combined with the effect of early up-front islet auto-transplantation in order to determine whether long-term endocrine function can be achieved.The online version contains supplementary material available at 10.1007/s00423-022-02468-x. Chronic pancreatitis (CP) is a debilitating disease. Patients suffer from a protracted disease course with serial episodes of recurrent pain. Abdominal pain serves as one of the cardinal hallmarks of CP . The paiThe management of CP remains a challenge. Historically, surgery was performed in the context of failed medical therapy . TherefoRecent advances in endoscopic techniques have resulted in novel approaches to managing CP . Main paThis systematic review and meta-analysis was performed with adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance . A broadTwo independent authors (DH and IH) performed screening of the individual titles and abstracts of the final search strategy against predefined inclusion and exclusion criteria. A full-text screen was subsequently performed. Any discrepancies were resolved by consensus following a discussion. The inclusion criteria consisted of studies that compared endoscopic intervention and surgery in the management of CP. In order to evaluate level 1 evidence as per the Oxford Centre for evidence-based medicine, only randomised control trials were included in this study . ArticleData extraction was performed by two independent authors (DH and IH), and the results were compared and discussed. A specific predesigned data collection pro forma was used for data collection. Data regarding the trial design and the demographics of patients included was collected. The nature of the surgical management (procedure performed) and the endoscopic intervention  was noted. Specific outcome measures were extracted and recorded: pain control, Izbicki score, exocrine and endocrine function. The primary outcome measure of this meta-analysis was the impact of either treatment (surgery or endoscopic intervention) on patients’ pain control. The use of a scoring system for pain control was recorded in addition as to whether the Izbicki score was utilised . The IzbMethodological quality and an assessment of bias for each included article were formally assessed using the Cochrane Collaboration tool for assessing risk of bias (RoB 2.0) . The oveI2 value. I2 value was considered to represent low (< 25%), middle (25–75%) or high degrees (> 75%) of heterogeneity. Results were deemed to be of statistical significance when p < 0.05.Data regarding predefined outcomes was summarised, grouped and formally analysed using the Review Manager  platform. Subsequent analysis of dichotomous variables was calculated utilising the odds ratio (OR) as the numerical statistic alongside 95% confidence interval (CI) with the Mantel–Haenszel method. Post-procedural pain relief, overall morbidity and mortality after surgery and endoscopy were analysed, alongside exocrine and endocrine dysfunction. Continuous data (such as Izbicki score) was assessed using mean difference (MD) and 95% CI with the inverse variance method. In order to account for clinical heterogeneity, the random effects model was used. Results were tabulated and visualised through forest plots. Assessment of heterogeneity amongst studies was assessed using the p < 0.001) .–32.29–32< 0.001) . All 3 t< 0.001) , 32. All< 0.001) , 29, 32.< 0.001) , 29, 32.A total of 267 patients with CP were included amongst the 3 RCTs  (Table p = 0.0008] with low heterogeneity (I2 = 0%). No difference was noted between either intervention for partial pain control  with low heterogeneity (I2 = 0%). A significantly higher rate of no pain relief was noted in CP patients following endoscopy (57/121 (47%) patients) when compared to surgical management (30/131 (23%) patients)  with low heterogeneity (I2 = 0%). This finding was reproduced when assessing the post-treatment Izbicki score following intervention. A significantly higher Izbicki score was noted in patients treated in the endoscopy arm at follow-up  with low heterogeneity (I2 = 0%). All three trials have a relatively small sample size. The trial by Díte et al. presents both a small randomised cohort of patients (endoscopic therapy 36 patients and surgery 36 patients) and a larger total group that encompasses both randomised and non-randomised patients [p = 0.01]. Higher rates of no pain relief occurred following endoscopic therapy (24/52 (46%) patients) when compared to surgical management (8/51 (16%) patients)   Table . Subgroupatients . We usedpatients . The finrol [OR 9% CI 1.13p = 0.06) [MD (95% CI) 3.57 (− 0.19 to 7.32)]. No significant difference was noted in the SF-36 mental health score following either intervention .The impact of surgery or endoscopy on quality of life was assessed by the results of the SF-36 questionnaire. The result of the questionnaire is on a scale that ranges from 0  to a 100 . For the effect on physical health, a trend towards surgery improving the physical health score was observed; however, this was not statistically significant  patients) or endoscopic therapy (49/124 (40%) patients) .In order to evaluate functional outcomes, the rates of new onset exocrine and endocrine failure following surgery and endoscopy were assessed. Of the two trials that reported on exocrine insufficiency, faecal elastase was utilised as a diagnostic test , 32. TheThis meta-analysis highlights that when compared to endoscopic therapy, surgery is associated with significantly higher rates of complete pain control at long-term follow-up . Furthermore, the outcome of the trial by Issa et al. demonstrates that early surgery (within 6 weeks of randomisation) resulted in lower pain scores at 18-month follow-up in comparison to the endoscopy first approach . From thSeveral different surgical approaches towards managing CP have been described over the decades. The definitive approach has yet to be determined. Heterogeneity of surgical practice is noted in this meta-analysis. A published network meta-analysis in 2020 of surgical strategies for CP demonstrated that the Beger procedure had the best ranking score for pain relief . HoweverAnother important discussion point is the frequency of treatment. Whilst surgery is definitive and provides treatment at a single time point within a hospital admission, this differs significantly to endoscopic therapy. Endoscopic management of CP will require serial interventions. The time course of treatment is prolonged and may significantly impact on the patient. Numerous hospital visits may have a detrimental effect on education or employment. Treatment for CP should allow for social re-integration rather than further isolation.A similar meta-analysis comparing endoscopic therapy and surgery for CP was published by Mendieta et al.; however, this meta-analysis did not assess endocrine/exocrine function or quality of life as treatment outcomes . QualityWhen investigating long-term functional outcomes, this meta-analysis failed to demonstrate a significant difference between new onset exocrine or endocrine failure following surgery or endoscopic management. However, the limitations of the included trials should be considered. Closer interrogation of the data demonstrates that 2 of the 3 included RCTs displayed higher rates of new onset endocrine failure following endoscopy , 32. HowThere are limitations to note within this meta-analysis. Long-term follow-up varied between the included RCTs, of which 2 reported 5-year follow-up data , 31. TheSurgical management is associated with superior pain control when compared to endoscopic therapy for CP and should therefore be considered first-line treatment. The evidence generated within this meta-analysis illustrates that significantly higher rates of complete pain control were achieved following surgery during long-term follow-up. A trend towards surgery improving physical health was observed. No statistical difference was noted between the rates of new onset exocrine or endocrine failure following either treatment strategy. Further research is required to determine the impact of early up-front TPIAT in patients with CP in order to assess whether prompt intervention following diagnosis can secure long-term endocrine function.Supplementary file1 (DOCX 2255 KB)Supplementary file2 (DOC 64 KB)Below is the link to the electronic supplementary material.


To study if pain relief after injection and arthroplasty correlate.n = 88; median age 64 (interquartile range (IQR) 22) years, 49 (56%) females) that received fluoroscopic-guided intra-articular hip injection with contrast agent, anaesthetic (diagnostic), and corticosteroid (therapeutic) before implantation of primary total hip arthroplasty. Pain scores were assessed pre-injection, post-injection after 15 min (diagnostic phase) at first clinical follow up  months), and postoperatively (last follow up (median 15 (IQR 5) months)). Responders had reduction in pain score ≥ 20  points. The primary outcome was the same (or inverse) response to injection and arthroplasty.A retrospective cohort study included consecutive patients (p < 0.001), therapeutic phase (50 (IQR 40) points; p < 0.001), and post-operatively (2 (IQR 15) points; p < 0.001). On the one hand, 69 (78%) cases had the same response in the diagnostic phase and post-operatively ; on the other hand 32 (36%) cases had the same response in the therapeutic phase and post-operatively . Furthermore, 57% and 91% of patients had an even better response post-operatively than in the diagnostic and therapeutic phases.The median pain scores were higher pre-injection (68 (IQR 30) points) compared to the diagnostic phase (18 (IQR 40) points; Pre-operative intraarticular injection can predict pain relief after primary total hip arthroplasty. A positive response to hip arthroplasty may be better predicted by the response to local anaesthetic (diagnostic phase) than corticosteroids. Most patients (91%) with osteoarthritis may expect better pain relief after arthroplasty compared to the therapeutic phase after injection. Intra-articular steroid injection for osteoarthritis of the hip is recommended by several international guidelines (e.g. European League Against Rheumatism) , 2. It iIf patients still continue to experience pain after injection(s) due to their hip osteoarthritis, they may opt to undergo total hip arthroplasty. The long-term outcome of total hip arthroplasty is very good and the satisfaction rates (92%) are usually superior to other common orthopaedic surgeries  and hallux valgus correction 77%)) [% and hal7%) [% anThis study hypothesized that pain relief after injection and arthroplasty correlate with each other. Furthermore, it was opted to find out if the response to hip arthroplasty can be better predicted by the diagnostic or therapeutic response to an injection.A retrospective cohort study was conducted at a single institution between 2016–2018. The local ethics committee provided a waiver for this study . This study was performed in accordance with relevant guidelines and regulations (Declarations of Helsinki).n = 88) that received fluoroscopic-guided intra-articular injection of the hip with a contrast agent, an anaesthetic (diagnostic), and corticosteroid (therapeutic) in 2016 before subsequent implantation of a primary total hip arthroplasty. In other words, all patients had an injection and hip arthroplasty, independent of the effect of the injection. Patients with a previous hip surgery (n = 10) were excluded. The median difference between injection and arthroplasty was 4 (IQR 6) months. The median follow-up was 15 (IQR 5) months.This study included all consecutive patients (Pain scores were assessed at baseline (pre-injection), after 15 min , at first clinical follow up (after median of 2 (interquartile range (IQR) 2) months; = therapeutic phase) post-injection, and at last follow up (after median of 15 (IQR 5) months) post-operatively. The scores were self-reported and obtained through chart review.The primary outcome parameter was the similarity of the response to diagnostic and therapeutic injection as well as arthroplasty (i.e. same direction of response versus (vs) different direction). Responders were defined as patients with absolute reduction in pain score ≥ 20  points, whereby the initially reported NRS from the radiology department (0–10) was multiplied by 10 .The diagnosis of osteoarthritis of the hip was based on self-reported pain at the hip and radiological evidence of osteoarthritis. Pain was graded on a numeric rating scale from 0–100 (worst) . OsteoarThe injection was performed in a standardized fashion similar to the protocol described before  after obData are provided as absolute numbers (percentages) and medians (IQR). The Wilcoxon matched-pairs signed-ranks test, McNemar’s test, and Spearman correlation were used using Stata/IC . Assuming an alpha of 0.05 and a difference in means on the NRS of 20 (standard deviation 20) points between responders and non-responders, 19 patients per group were needed according to a previous calculation by Atchia et al. .n = 88). The median Kellgren and Lawrence osteoarthritis grade was 3 (IQR 1).The median age was 64 (IQR 22) years and there were 49 (56%) females (p < 0.001), in the therapeutic phase (50 (IQR 40) points; p < 0.001), and post-operatively after a median of 15 (IQR 5) months (2 (IQR 15) points; p < 0.001) .The median pain scores were higher at baseline (68 IQR 30) points) compared to the diagnostic phase (18 (IQR 40) points; 0 points)p < 0.001). Furthermore, 57% and 91% of patients had a better response to hip arthroplasty than the diagnostic and therapeutic phases, respectively. For the diagnostic phase, the sensitivity was 83%. For the therapeutic phase, the sensitivity was 33%.Sixty-nine (78%) cases had the same response post-injection in the diagnostic phase and post-operatively (rho = 0.58), compared to 32 (36%) cases with the same response in the therapeutic phase and post-operatively (rho = 0.25) (p = 0.458) and in the therapeutic phase in two (2%) patients (p = 0.797).A response (i.e. absolute pain reduction ≥ 20 points) was found post-operatively, but non-response was seen in the diagnostic phase in 14 (16%) patients and in the therapeutic phase in 54 (61%) patients. Contrarily, a non-response was found post-operatively, but a response was observed in the diagnostic phase in five (6%) patients  between pain relief in the diagnostic phase after cervical nerve root blocks and around two years after decompression in 33 patients [Up to this study, it had been mostly unknown if the pain relief from injections correlates with the one from hip arthroplasty. To the best of our knowledge, there is only one older study with 42 patients by Crawford et al., which reported that 78% of patients had pain relief from their injection of diagnostic local anaesthetic and 96% had subsequent successful total hip arthroplasty after a minimum of six weeks . Most patients  with osteoarthritis may expect even better pain relief after total hip arthroplasty compared to the therapeutic phase after injection.


Before the planned second injection, the patients received topical bromfenac eye drops twice a day for 3 days. At 1, 6, and 24 h after the first and second injections, the post-injection pain scores were determined using the numerical rating scale (NRS) telephonically. (3) Results: A total of 28 patients were enrolled in this study. After the first intravitreal injection, the NRS pain scores were 4.04 ± 1.90 at 1 h, 1.57 ± 1.75 at 6 h, and 0.93 ± 1.27 at 24 h. The pain scores after the second intravitreal injection significantly decreased at each measurement time point ( Intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection therapy is widely used for the treatment of retinal vascular diseases. Since the therapeutic drug is directly injected into the eye, it acts quickly and is effective. However, as it is an invasive treatment, patients may experience pain or discomfort during or after the injection or may be afraid of the injection treatment. In addition, since multiple injections are often required, the pain and discomfort experienced by patients cannot be overlooked .Pain that may occur during intravitreal injection therapy has been investigated and reported to be reduced with the concomitant use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) ,3,4. NSAAdministration of nepafenac eye drops after intravitreal injection was shown to improve ocular discomfort . In partFactors related to pain associated with intravitreal injection therapy include age, sex, and number of injections taken in the past. Older patients, women, and patients who have received several injections have low pain scores . ExistinThis study aimed to analyze the efficacy of pretreatment use of preservative-free bromfenac eye drops in relieving pain after intravitreal anti-VEGF injection treatment.This single-center, prospective, non-randomized, unblinded pilot study was conducted in accordance with the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Severance Hospital . The inclusion criteria were as follows: (1) patients with planned intravitreal anti-VEGF injections , ranibizumab , or aflibercept ) at least 2 times and (2) patients more than 20 years old. The exclusion criteria were as follows: (1) patients with other eye diseases that may cause ocular pain ; (2) patients who had difficulty in understanding and responding to the questionnaire because of severe cognitive, communication, and perception problems; and (3) patients aged below 20 years old.In order to calculate the minimum number of subjects as a previous study for clinical trials, another paper on a similar subject was referred . Using GAfter providing informed consent, all patients underwent history taking, corrected visual acuity and intraocular pressure measurement, slit-lamp and fundoscopic examination, and optical coherence tomography at the screening visit. The patients were scheduled for at least two consecutive intravitreal anti-VEGF injections, and telephonic questionnaires were used to quantify pain after 1 h, 6 h, and 24 h. Injection treatment was performed by the same doctor (D.H.L.). The injection treatment procedure was as follows: After instillation of 0.5% proparacaine hydrochloride  eye drops, the eyelids and conjunctival sac were sterilized and flushed with 5% povidone iodine. Then, the eyes were opened using the eyelid speculum. After instillation of 0.5% proparacaine hydrochloride  eye drops, 0.05 cc of anti-VEGF agent was injected into the inferotemporal or inferonasal area 3.5 mm posterior from the corneal limbus through a pars plana using a 30G needle. Topical moxifloxacin eyedrop  was instilled, and the eyelid speculum was removed. Since the injection treatment was performed on the same day as the patients’ outpatient visit, the injection timing of the patients was not the same. Before the planned second injection, the patients received topical bromfenac eye drops twice a day for 3 days. At the next visit, the examinations performed at the screening visit were repeated, and the pain scores after intravitreal anti-VEGF injection treatment were determined telephonically using the numerical rating scale (NRS). During the telephone questionnaire after the injection, the patients were asked whether they had redness, pain, decreased vision, or other discomfort, and additionally, whether other adverse reactions or symptoms occurred were checked at each outpatient visit.Pain scores determined using the NRS were the primary outcome, and complications related to injection treatment or pretreatment topical bromfenac instillation were the secondary outcomes.p-value of <0.05 was considered statistically significant.Statistical analyses were performed using SPSS Statistics v25.0 . Descriptive analysis was performed and the paired t-test and Wilcoxon’s rank-sum test were performed to analyze the change in pain scores after injection treatment. The pattern of changes in the pain scores after injection treatment was analyzed using a one-way repeated measures analysis of variance. A This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.®, Bayer, USA) in 15 patients (53.6%), bevacizumab  in 10 patients (35.7%), and ranibizumab  in 3 patients (10.7%). There were 2 treatment naïve patients, and the remaining 26 patients received an average of 10.8 ± 10.4 injections  were men. Twelve patients had a history of hypertension and diabetes, and 11 had a history of diabetes. The diagnoses of the patients were as follows: age-related macular degeneration (AMD) in 21 patients (75.0%), diabetic macular edema (DME) in five patients (17.8%), AMD with DME in one patient (3.6%), and macular edema secondary to branch retinal vein occlusion in one patient (3.6%). Patients were followed up for an average of 82.7 ± 77.9 days. The drugs used for treatment were as follows: aflibercept (Eyleajections .p < 0.001). After the pretreatment use of topical bromfenac eye drops for 3 days, the pain scores determined telephonically showed a significant decrease over time (p < 0.001). A comparison of the pain scores between the first injection treatment without bromfenac eye drops pretreatment and second injection treatments with bromfenac eye drops pretreatment showed that the pain scores decreased significantly after 1 and 24 h . The pain score 6 h after injection treatment was lower after the first injection treatment than after the second injection treatment, but the difference was not statistically significant (p = 0.055, The change in pain scores was analyzed at different time points after the injection treatment. The pain scores after injection treatment determined telephonically showed a significant decrease over time (During the study period, no patients required additional visits or treatment for complications related to the intravitreal injection treatment.The results of this study showed that after administering bromfenac eye drops before intravitreal injection treatment, the pain scores after intravitreal injection treatment improved significantly. No adverse events associated with the use of bromfenac eye drops before intravitreal injection therapy were observed.Several studies have assessed the pain that may occur during or after intravitreal injection therapy. Ulrich et al.  found thPain scores after the topical bromfenac instillation were lower in old patients, female patients, and patients who had received multiple intravitreal injections than young patients, male patients, and patients who had received no or single intravitreal injections . In thisIn particular, using topical bromfenac before intravitreal injection can reduce patient anxiety . AlthougComplications that may occur with the use of topical bromfenac eye drops include ocular irritation, though serious complications such as corneal epithelial issues occur rarely . In thisThis study has several limitations. First, this study was conducted with a relatively small number of patients, and the time interval between the first and second injections was not consistent. Another limitation is that injection drugs and causative diseases are heterogeneous, which may have affected the pain reduction effect of bromfenac. In addition, there is no control group that did not use bromfenac eye drops in this study. Since the patients were informed that the pain relief effect after using bromfenac eye drops was to be analyzed, it is possible that the pain score after the second injection treatment was lower due to the expectation of the pain relief effect of the patients . In a fuIn conclusion, the pretreatment use of preservative-free bromfenac eye drops in patients undergoing intravitreal injection therapy can significantly improve the post-injection pain scores and patient compliance with intravitreal injection therapy. In addition, this study can serve as a basis for the design of a large-scale randomized comparative study.


Chronic pain management multi/interdisciplinary programs attempt to address all elements of the biopsychosocial model. The primary objective of this retrospective study (based on practice-based audit) was to determine the effectiveness of a patient-centered, comprehensive and intense interdisciplinary pain management program in a publicly funded community-based pain clinic in the Greater Toronto Area.This retrospective longitudinal study was conducted on 218 carefully selected sequential chronic pain patients, with 158 completing a 3–4-month interdisciplinary program between January 2016 and December 2018. Data collected upon exit, at 6 months and 12 months post-discharge included demographic information, pain characteristics, emotional/functional status obtained by validated instruments and global impression of change (GIC). Additionally, social health outcomes (return to work or school) were retrieved through retrospective chart review. Means of pre-and post-program variables were compared to assess changes of each patient’s “journey”.Physical and mental/ emotional health outcomes at exit, 6 months and 12 months post-discharge, showed initial and sustained, statistically and clinically significant improvement from pre-treatment levels, with GIC (much/very much improved) reported as 77%, 58% and 76%, respectively. Additionally, a substantial positive change in social health outcomes was noted particularly in patients on disability (29%), part time workers gaining full time employment (55%), and students (71%) who improved their level of schooling.The study showed that careful patient selection in a community-based publicly funded interdisciplinary pain management program can produce significant improvement in pain, physical, mental/emotional health and social function, with sustained long-term outcomes. Chronic pain is a major societal issue. One in 5 people in Canada suffer from chronic pain  with est2, the biopsychosocial model of pain and disability (first introduced by Engel 1977) [While the biomedical reductionist model of treating chronic pain conditions is outdatedel 1977) .multidisciplinary versus interdisciplinary pain management. While both types of programs use multimodal treatments and a variety of clinicians, the latter is characterized by shared common rehabilitation philosophy, robust ongoing communication between health care professionals, and active patient involvement. Schatman [The biopsychosocial model has led to the development of a multifaceted assessment and treatment paradigm of chronic pain . GatchelSchatman , summariSchatman , 6.Review of the literature demonstrates great variability in inclusion/exclusion criteria for admission to pain management programs. Bosy et al.  includedIn Ontario (the largest province of Canada), the Ministry of Health and Long Term Care (MOHLTC) created in 2011 a Chronic Pain Working Group which produced a White (policy) Paper, pointing to a long number of problems in the province and outlined the essential elements needed to support a comprehensive pain system. Details of the process have been published elsewhere .In 2014, MOHLTC provided $18 M CAD in base funding to support interdisciplinary chronic pain management in Ontario across five pediatric hospitals, 13 adult hospitals, and one community chronic pain clinic . Since MOHLTC has indicated they plan in the future to expand funding outside the academic hospital network to community settings, PWC patient outcomes are of great importance to MOHLTC for future policies.2 with a population of 5.93 M. The PWC offers pain consultations, recommendations and/or medical management to patients referred by community family doctors and specialists, as well as interdisciplinary pain management (IDP) to a select group of chronic pain patients considered appropriate candidates  of our interdisciplinary pain management program in an effort to ascertain its long-term effectiveness and assist MOHLTC in future policy and funding decisions. The primary objective of this study, therefore, was to determine the effectiveness of our community-based interdisciplinary pain management program. The study is unique in the sense that it is (a) pragmatic, evaluating the effectiveness of interventions in real-life routine practice conditions; while (b) funding of the interdisciplinary program is not an obstacle as it is provided by MOHLTC, which allows us to select all the patients who meet our eligibility criteria. Lack of funding is considered one of the most important barriers in provision of interdisciplinary pain management programs, a factor thankfully absent from the present study .The current study is a retrospective longitudinal pragmatic study of 218 consecutive new patients offered admission to the IDP over a 3-year period (January 2016–December 2018), with the data arising from an internal audit. The study was approved for retrospective analysis by the University of Toronto Research Ethics Board . Patients were derived from the general population of patients seen in PWC and met the following criteria published in a previous study [The study population was derived from the general population of pain patients referred to the PWC for a medical pain consultation. All patients are evaluated by a physician and another team member through an exhaustive history and thorough physical examination; 1–2 patients out of 5 meet established eligibility criteria and are offered admission to our IDP. These patients suffer mostly from myofascial or mechanical pathology, as well as from emotional and cognitive issues secondary to persistent chronic pain, poor coping mechanisms, poor understanding of mind/body interactions etc.The PWC IDP treatment program is patient centered, interdisciplinary and based on the shared decision-making model . It provData collection for the study population was electronic, overseen by staff at the time of the intake interview and included (a) demographics such as age, sex, marital status, work status, country of birth and education; (b) individual scores of validated questionnaires at baseline, exit and 6 and 12 months post exit ; and (c) social health outcomes , the latter through retrospective chart review, documenting social status at the time of entry to the program vs social status at 6 and/or 12 months. Multiple reminders were sent to patients regarding completion of the questionnaires at 6 and 12 months after program exit. Follow up medical visits continued after exit from the IDP .Based on the literature on chronic pain management outcomes , a numbeThe validated questionnaires we used included the following: pain catastrophizing scale (PCS) ; pain seFurthermore, in this study, we extended our efforts to extract social health data relating to patients’ work or school status, which could not be captured by the questionnaires we cited above. Such information could only be obtained through retrospective chart review as the vast majority of patients continued visiting the physicians in our centre. The impact of pain in the workplace is an important issue to be considered in chronic pain patients. Studies carried out in different countries have shown that patients who are affected by pain have high levels of work absenteeism. Not only must they often change their occupational duties or post, but they may even end up losing their job as a result of their pain symptoms . Patientminimally important improvement; a decrease ≥ 30% as a moderately important improvement; and a decrease ≥ 50% as a substantial improvement according to the main IMMPACT outcome recommendations [The mean BPI pain intensity  and pain interference scores were divided into three categories. A 10–20% decrease in pain intensity and pain interference over the 3 months of the program was considered as a ndations .2 test or Fisher’s exact tests and t-tests, were used. For the ratio analysis χ2 goodness-of-fit test was used. At 95% confidence interval, the two-sided p value of < 0.05 was used to define minimal statistical significance. When the denominator is different due to missing data, the exact number will be indicated in brackets. Means (± SD) of pre-and post-program variables were compared to assess effectiveness of program progress. The percent change in pain intensity and functional and emotional scores was calculated as the difference of mean between baseline, 6 and 12 months.All data were analyzed using SPSS . Descriptive statistics were used for demographics, pain, diagnostic groups, and opioid data. The descriptive analysis consisted of means and proportions according to the nature of the variables. For categorical data, proportion and size of each category for all demographic characteristics , and body map areas, were calculated. Means and standard deviation were computed as well for pain characteristics , opioid dosages and validated questionnaire outcome measures. For statistical comparison of categorical and continuous variables, Pearson χA total of 218 patients were enrolled in the IDP and 169 completed the program (completers). Of note, 11 out of 169 completers, did not provide exit questionnaires for various reasons and only their demographic and entry data were used for parts of the analysis. Therefore, exit data analysis was done on n = 158 datasets. Unfortunately, a number of patients could not be located/ contacted despite email, text and phone attempts, or did not fill the forms even when they received verbal, telephone and email reminders, so returned questionnaires for 6 and 12 months were 66 and 46, respectively.We noted the following for the entire cohort N = 218): female predominance ; mean age 45 +/− 16; pain duration 8 ± 8 yrs (range 1–35 years); 12% were > 65 years of age; 62% were Canadian born (CB); 13% had chronic pain due to disease ; and 68% of the patients had sustained some form of compensable trauma with legal involvement . Details are presented in Table 8: femaleForty four patients of the 218 enrolled patients, started but failed to complete the program (non-completers) for the following reasons: Multiple No Shows or Late Cancellations (n = 12); Limited availability due to work or other life commitments (n = 8); Medical reasons (n = 6); Interruption due to life crisis that occurred after entry to the program (n = 5); Dismissed by program due to non-compliance (n = 6); Patients dropped out on their own volition (n = 7). Another 5 patients who were enrolled and completed the entry battery, never showed up to start the program (n = 5). Altogether, the non-completer group consisted of 49 patients. With the exception of those patients who interrupted the program due to medical reasons (n = 6), the remaining 43 patients provide a measure of “non-compliance” for reasons cited above. The patients (n = 169) who entered the program and completed it fully were obviously the “compliant and adherent” group.p < 0.05) between Canadian Born (CB) versus Foreign Born (FB). The CB/FB ratio was 2/1 for completers (similar to that reported by Canadian Census for GTA), and 1/1 for non-completers of CB/FB due to significant increase of FB in the latter subgroup  and pain interference (arithmetic mean of the seven interference items) Table .Table 2MIn terms of physical and mental/emotional health outcomes, improvement  was noted in completers across all validated scales at exit. Percent change (indicating improvement) between entry and exit scores of all completers was as follows: Pain catastrophizing 46%; Pain self-efficacy 52%; anxiety 40%; depression 50%; kinesiophobia 15%; BPI pain severity 29%; and BPI pain interference score 40% Tables , 4. TablTable Improvement ≥ 50% was experienced at exit by 30% of patients on BPI pain severity score and 41% of the patients on BPI interference score, while worsening of pain score and pain interference was noted in 14% and 16%, respectively . Significant social status improvement was noted in 29% of the patients classified upon entry as disabled, 55% of the part time workers, 71% of students and 75% in the small group of those under the miscellaneous group. Naturally, the social status of homemakers and retirees did not change , while 8% of those who were working full time jobs upon entry to the program got (self-reported) better employment. The results are detailed in Table This study presents long-term data (up to 12 months post-graduation) from a series of well selected chronic pain patients admitted to a Canadian community-based, comprehensive, one-to-one, interdisciplinary pain management program funded by MOHLTC. The study population consisted of middle age, well-educated chronic pain patients , with a high proportion of employment  is consistent with that reported in the literature 17–57%) [–57% 7, , 22. The.4% is coThe poor completion rate of validated batteries at 6 and 12 months is a well-known phenomenon and has been reported in pragmatic practice-based clinical studies , 8, 23. The slight drop in the subjective GIC “much/ very much improved” scores at the 6-month period after program termination and subsequent improvement to exit levels at 12 months, has been observed in other programs. While the reduced number of returned questionnaires at 6 and 12 months may have skewed the results, we did review our raw data and realized that depression and anxiety had increased at 6 months (accounting for the GIC drop), consistent with the hypothesis of an “adjustment period”  until skOur IDP program meets all the criteria of a well-functioning interdisciplinary pain program , summarized by Stanos  as folloOur thematic analysis (IASP poster 2020)  has showOur eligibility criteria have evolved over time after we observed during the first months of the program high drop-out rates in patients with severe untreated or poorly treated psychopathology or presence of life crisis (though the latter can still happen in the midst of the program as our data show). Besides absence of psychopathology, patient motivation is a primary driver for admission, judged not through formal questionnaires, but during a detailed 2–2.5 h team assessment, and if required, review by a psychologist before the patient is accepted to the program. Given the high number of foreign-born patients in the non-completer group, we now pay more attention to family obligations and support that may vary based on cultural background. Our eligibility criteria ultimately are very similar to those of Knight et al. .Existing literature shows considerable variability in interdisciplinary pain management programs in regard to eligibility criteria, program duration, treatment service provision, mode of treatment administration , funding of the services, numbers of treatment hours etc. , 23, 25.Deckert et al.  conducteClearly our program provides long term outcome data on all three domains .Our patient selection criteria result in selection bias, as we enrol the best patients that can benefit from our program.Since MOHLTC funding is limited to a single community-based pain management program (ours), our results are not generalizable to other pain management facilities that depend exclusively on third-party funding as such programs are costly and third parties must approve funding. Therefore, many pain patients who can benefit from these treatments can not access them.Our program offers nearly exclusively one-to-one in-person treatment. In contrast, the vast majority of programs reported in the literature offer mostly or exclusively group sessions in-person, and some partial or exclusive virtual group sessions. In this context, it would be difficult to exactly duplicate our treatment model.Treatment services and hours in our program vary substantially from 60 h (for 3 different forms of treatment) to 120 h . The program is totally customized for each participant and tailored to specific patient needs and goals. Such customization is not possible in many interdisciplinary pain management programs.Our patients have access to the physicians on site for their medical needs during the program, while they have follow-up visits (regular or as needed) after they exit the program. This provides continuity of care and contrasts many other interdisciplinary programs where follow ups in general are limited or terminate shortly after the program ends.Furthermore, the decreased numbers of returned questionnaires at 6 and 12 month may have limited the validity of the follow-up analysis . This phenomenon plagues pragmatic practice-based studies, and we attempt harder now to address it by intensifying our telephone, email and text reminders.Limitations of the study given the specific structure of our program limiting generalizability are:Careful patient selection in a publicly funded, patient-centered, comprehensive and intense interdisciplinary pain management program produces significant improvement in pain, physical, mental/emotional health and social function, with sustained long-term outcomes .While most interdisciplinary pain management programs are conducted in large tertiary care academic settings, our study shows that such programs can be successfully delivered in a community setting, while secure funding ensures treatment of all eligible patients and not just those “who can afford” the program.Our study model and results have wide implications for MOHLTC policymakers in their effort to reduce personal suffering and the economic burden of chronic pain by expanding public funding to community-based pain clinics in Ontario.


Currently available medications for chronic osteoarthritis pain are only moderately effective, and their use is limited in many patients because of serious adverse effects and contraindications. The primary surgical option for osteoarthritis is total joint replacement (TJR). The objectives of this study were to describe the treatment history of patients with osteoarthritis receiving prescription pain medications and/or intra-articular corticosteroid injections, and to estimate the incidence of TJR in these patients.This retrospective, multicenter, cohort study utilized health plan administrative claims data  of adult patients with osteoarthritis in the Innovation in Medical Evidence Development and Surveillance Distributed Database, a subset of the US FDA Sentinel Distributed Database. Patients were analyzed in two cohorts: those with prevalent use of “any pain medication”  using only the first qualifying dispensing (index date); and those with prevalent use of “each specific pain medication class” with all qualifying treatment episodes identified.Among 1 992 670 prevalent users of “any pain medication”, pain medications prescribed on the index date were NSAIDs (596 624 [29.9%] patients), opioids (1 161 806 [58.3%]), and intra-articular corticosteroids (323 459 [16.2%]). Further, 92 026 patients received multiple pain medications on the index date, including 71 632 (3.6%) receiving both NSAIDs and opioids. Altogether, 20.6% of patients used an NSAID at any time following an opioid index dispensing and 17.2% used an opioid following an NSAID index dispensing. The TJR incidence rates per 100 person-years  were 3.21 (95% CI: 3.20–3.23) in the “any pain medication” user cohort, and among those receiving “each specific pain medication class” were NSAIDs, 4.63 (95% CI: 4.58–4.67); opioids, 7.45 (95% CI: 7.40–7.49); and intra-articular corticosteroids, 8.05 (95% CI: 7.97–8.13).In patients treated with prescription medications for osteoarthritis pain, opioids were more commonly prescribed at index than NSAIDs and intra-articular corticosteroid injections. Of the pain medication classes examined, the incidence of TJR was highest in patients receiving intra-articular corticosteroids and lowest in patients receiving NSAIDs.The online version contains supplementary material available at 10.1186/s12891-022-05823-7. Recent estimates suggest that about 528 million people worldwide have osteoarthritis (OA) of the hip, knee, hand, shoulder, foot, or other sites . ChronicThe 2019 guidelines of the American College of Rheumatology/Arthritis Foundation recommend NSAIDs as first-line oral pharmacotherapy for OA pain, at the lowest doses and shortest durations possible because of the risk of adverse cardiovascular, gastrointestinal, and renal side effects. The guidelines only conditionally recommend tramadol versus other opioids, noting the modest benefits and high risk of adverse effects with long-term opioid use ) unless censored by the first occurrence of any of the following: disenrollment, death, end of the available data , or TJR event.We also estimated the incidence of TJR during the treatment duration for the “each specific pain medication class” cohort. The follow-up period began on the index date and continued until the first occurrence of any of the following: disenrollment, death, end of the available data, end of the query period, TJR event, discontinuation of treatment, or initiation of a pain medication from a different drug class.TJR events were identified by International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9-CM/ICD-10-CM) diagnosis codes and/or Current Procedural Terminology codes appearing in claims of any encounter setting, including inpatient, institutional stay, and ambulatory claims. Assessment of TJR did not differentiate knee versus hip TJR events among pain medication users in this analysis. Distributed analyses were performed using the publicly available Sentinel analytic toolkit  .A total of 1 992 670 prevalent users of “any pain medication” were identified between January 1, 2013, and December 31, 2019. Demographics and baseline clinical characteristics for the “any pain medication” cohort are shown in Table Among the “any pain medication” users, history of ≥ 1 dispensing of NSAIDs was noted in 45.5%, opioids in 62.6%, and intra-articular corticosteroids in 25.0% of patients during the entire available history prior to index date  patients received NSAIDs, 1 161 806 (58.3%) received opioids, and 323 459 (16.2%) patients received intra-articular corticosteroids  was 3.21  were 4.63 (95% CI: 4.58–4.67) for NSAIDs, 7.45 (95% CI: 7.40–7.49) for opioids, and 8.05 (95% CI: 7.97–8.13) for intra-articular corticosteroids, during the treatment duration, with a 30-day extension to the end of the treatment episode for the NSAID and opioid users, and using a 90-day exposure duration and 30-day extension for those receiving intra-articular corticosteroids , complementary and alternative medicines, and homeopathic remedies. Further, chronic pain may be a driver for increased health care utilization, and we would expect to see increased utilization among those with chronic pain . In addiAmong this population of nearly 2 million individuals in the United States receiving prescription medications for OA pain from 2013 until the end of 2019 (prior to the COVID-19 pandemic), opioids were more commonly used than NSAIDs and intra-articular corticosteroid injections. Further, 41% of opioid users and 30% of NSAID users at index date subsequently received a different class of pain medication. Of the specific pain medication classes examined, the incidence rate of TJR was highest in patients receiving intra-articular corticosteroids and lowest in patients receiving NSAIDs.Additional file 1: Supplementary Table S1. Demographics and baseline clinical characteristics for prescription pain medication recipients in the “each specific pain medication class” cohort.Additional file 2: Appendix D. List of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM), International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), and Current Procedural Terminology, Fourth Edition (CPT-4) Procedure Codes Used to Define the Outcome (Aims 1-3) and Exposure (Aim 4) in this Request.