Background: Chronic non-cancer pain (CNCP) is a prevalent condition, imposing significant burden on healthcare systems. Ketamine is suggested as a potential intervention for CNCP management. We conducted a systematic review and network meta-analysis to assess ketamine's effects in adults with CNCP. Methods: We searched Medline, Embase, CINAHL, and Cochrane CENTRAL up to January-2024 for randomized trials involving adults with CNCP, comparing ketamine with placebo, usual care, or other interventions. Reviewers independently assessed trial eligibility, extracted data, and evaluated risk-of-bias using the Cochrane tool. A random-effects network meta-analysis was performed. We assessed evidence certainty using GRADE. Results: We included 38 trials, with the following comparisons made between ketamine and placebo, using 0-10 VAS: At <30 minutes, ketamine may slightly reduce pain intensity (-1.32, 95% CI: [-1.73 to -0.90], low-certainty). At 1-3 hours follow-up, ketamine may slightly reduce pain intensity (MD: -1.25, (95% CI: [-1.76 to -0.74], low-certainty). At 3-to-7 days follow-up, ketamine may have little to no effect on pain intensity (MD: -1.34, 95% CI: [-2.29 to -0.39], low-certainty). At 3-to-5 weeks follow-up, ketamine likely results in no pain reduction (MD: -0.99, 95% CI: [-2.00 to 0.03], moderate-certainty). At beyond 5 weeks the evidence about ketamine pain reduction is very uncertain (MD: -1.09, 95% CI: [-1.86 to -0.32], very-low-certainty). Ketamine had no effect on physical functioning. Compared to placebo, ketamine may result in a slight increase in the risk of gastrointestinal adverse events (RR: 3.97, 95% CI: [2.18 to 7.22], RD: 12%, 95% CI: [5% to 25%], very-low-certainty), an increase in risk of dizziness (RR: 3.66, 95% CI: [1.25 to 10.74], RD: 11%, 95% CI: [1% to 40%], low-certainty), may increase the risk of fatigue, somnolence, and sedation (RR: 2.89, 95% CI: [1.84 to 4.53], RD: 27%, 95% CI: [12% to 50%], low-certainty), may increase of the incidence of dissociative symptoms (RR: 4.22, 95% CI: [2.20 to 8.10], RD: 17%, 95% CI: [6% to 37%], low- M.Sc. Thesis – Sara Moradi; McMaster University – Health Research Methodology iv certainty), and it may result in a slight increase in the risk of visual impairment (RR: 10.21, 95% CI: [2.86 to 36.42], RD: not evaluable, very-low-certainty). We did not have enough data to pool effect estimates for other outcomes. Conclusion: Ketamine may provide small but important benefit in CNCP patients at immediate-to-short follow-up, but it probably has little to no benefit at beyond 3-weeks. Ketamine is likely to provide similar benefits compared to alternative active interventions; however, these benefits may be associated with important side-effects. / Thesis / Master of Science (MSc)

Pain has been described as the most complex human experience and most frequent reason patients seek medical treatment. Few people fail to experience the pain associated with disease, injury, or medical/surgical procedures. However, the impact of unemployment that results from chronic pain suffering has not been widely researched. To present a comprehensive view of the effect unemployment has upon the chronic pain experience, this study focused upon stress philosophy, chronic pain, employment, and coping effectiveness. The Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), and a Personal Data Questionnaire (PDQ) were administered to 96 persons (four groups of 24 subjects) representing either unemployed or employed and either chronic or non-chronic (acute) pain populations.

This study investigated the relationship between preferred coping strategies, and major stressors for nondepressed, and depressed chronic pain patients. The subjects for this study were 67 chronic pain patients who are participating in a pain/spinal rehabilitation program. The information collected from the individuals or their records included: (1) basic demographic information, (2) level of activity, (3) level of perceived pain, (4) medication usage, (5) therapist rating of level of stabilization, (6) scores on three inventories including the Coping Strategies Questionnaire, the Ways of Coping Checklist, and the Beck Depression Inventory. Analyses included an examination of the relationship between level of depression and (1) type of stressors, (2) coping strategies, and (3) level of perceived pain. Further analyses included multiple regression with outcome as defined by therapist ratings at the end of treatment, and patients' ratings at follow up as the criterion variables.

Objective: P300/CBP Associated Factor (PCAF) is a histone acetyltransferase, and has been reported to interact with nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and to stimulate cyclooxygenase-2 (COX-2) transcriptional activation. The aim of this study was to determine the role of PCAF in chronic pain modulation. / Method: In an in vitro experiment, PCAF small-interfering RNA (siRNA) was used to knock down PCAF. Interleukin-1 β (IL1β) was applied as COX-2 inducer in SK-N-SH neuroblastoma cells. Luciferase assay and chromatin immunoprecipitation (ChIP) were performed regarding COX-2 promoter region. / In an in vivo experiment, PCAF was examined for its distribution in dorsal horn of Spraque-Dawley rats. COX-2 level in the spinal cord was determined after inhibition of PCAF in rats with Complete Freund's Adjuvant (CFA)-induced pain. ChIP was also performed. / Finally, we tested whether genetic variations in the PCAF gene affected the risk of chronic pain in a gene association study of 267 surgical patients. The associations of pain with genotypes (58 single nucleotide polymorphisms, SNPs)/haplotypes were analyzed by χ² and Fisher exact tests. / Results: Knock-down of PCAF reduced COX-2 level and NF-κB activity. PCAF and acetylated histone 3 lysine 14 (H3K14) were enriched at COX-2 promoter when IL1β was applied. / PCAF was expressed in neurons at superficial layers of rat dorsal horn. In the in vivo experiment, COX-2 was reduced with the inhibition of PCAF in CFA rats. PCAF was enhanced at COX-2 promoter when CFA was injected. Anacardic acid and PCAF siRNA significantly alleviated thermal nociception and mechanical allodynia. / In the gene association study, 6 SNPs and 5 haplotypes were significantly associated with higher risk of severe chronic postsurgical pain. Multivariable analysis showed that patients with a SNP rs6763504 had a higher risk of developing severe chronic postsurgical pain (p = 0.001). / Conclusion: PCAF regulated COX-2 transcription and reduction or inhibition in PCAF resulted in a decrease in COX-2 and less chronic inflammatory pain. Genetic variations in the PCAF gene increased risk of severe chronic post-surgical pain in patients. / 實驗目的：P300/CBP相關蛋白（PCAF）是一種組蛋白乙酰化轉移酶。這種蛋白已被報道可以和核因子活化B細胞κ輕鏈增強子(NF-κB)相互作用，以及增進環氧合酶-2（COX-2）的轉錄激活。本實驗的目的在於研究PCAF在疼痛調節中的作用。 / 實驗方法：在細胞實驗中，我們使用了小干擾RNA（siRNA）來降低PCAF的含量。同時我們使用了白細胞介素-1β（IL1β）來作為SK-N-SH神經母細胞瘤細胞中COX-2的誘導劑。我們使用了熒光素酶試劑和染色質免疫沉澱來研究COX-2啟動子區域。 / 在體內實驗中，我們檢測了PCAF在大鼠脊椎背角部位的分佈。在弗氏完全佐劑（CFA）致痛的大鼠模型中，我們在PCAF抑制的情況下檢測脊髓中COX-2的水平。我們還進行了染色質免疫沉澱。 / 最後，在招募了267位手術患者的基因關聯試驗中，我們對PCAF基因中的基因變異對慢性疼痛風險的影響進行了分析。我們運用卡方檢驗和費雪精確性檢驗對疼痛與基因型（58個單核苷酸多態性）和單倍型的關係進行分析。 / 實驗結果：減少的PCAF降低了COX-2的水平以及NF-κB的活性。當添加了IL1β時PCAF和乙酰化第三組蛋白14號賴胺酸（H3K14）在COX-2啟動子處富集。 / PCAF在大鼠脊椎背角部位的淺表層（第一層和第二層）的神經細胞里表達。在動物實驗中，注射了CFA的大鼠顯示COX-2會隨著PCAF的抑制而下降。大鼠注射了CFA后PCAF在COX-2啟動子處有所增加。漆樹酸和PCAF siRNA顯著地減輕了熱痛和機械痛提高了機械痛閾值。 / 在該基因關聯試驗中，我們鑒定出六個單核苷酸多態性和五種單倍型與較高風險的嚴重術後慢性痛有顯著的相關性。多元回歸分析表明在PCAF基因上具有rs6763504遺傳變異的病人在術後發展嚴重慢性痛的幾率會較高(p = 0.001)。 / 結論：PCAF調節COX-2的轉錄，而且PCAF的減少或者抑制導致了COX-2的降低同時慢性炎症痛的減少。PCAF基因上的遺傳變異提高了術後病人嚴重慢性痛的風險。 / Meng, Zhaoyu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 117-134). / Abstracts also in Chinese. / Title from PDF title page (viewed on 30, December, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

The current research examined the proposition that individuals who were securely attached had a fundamentally different reaction and experience of chronic pain to the experience of individuals with an insecure attachment style. A biopsychosocial model of chronic pain was created that included the variables of attachment style, pain, depression, anxiety, somatisation, quality of life, function, disability, neuroticism, age and gender. Three cross-sectional quantitative studies and one qualitative study were conducted. Participants were (a) patients from a multidisciplinary pain centre in a major public hospital, and (b) members of the general population with chronic pain who were recruited from both urban and rural settings, across various community support groups. The total sample was 470. Instruments for the quantitative studies included the Revised Adult Attachment Scale (Collins & Read, 1990), the McGill Pain Questionnaire (Melzack, 1975), the Pain Patient Profile (Tollinson & Langley, 1992), the Quality of Life Inventory (Frisch, 1994), the International Association for the Study of Pain Assessment Protocol (International Association for the Study of Pain, 1986), the Migraine Disability Scale (Stewart, Lipton, Kolodner, Liebermann, & Sawyer, 1999), and the short form of the Eysenck Neuroticism Scale (Eysenck, Eysenck, & Barret, 1985). The clinical and non-clinical participants with a diagnosis of chronic pain syndrome were partitioned as securely or insecurely attached. In the clinical sample, the proportion of securely attached individuals was less than one quarter of the group, while in the non-clinical sample the proportion of individuals in the securely attached group was 50%. For Study 1, (200 individuals from the clinical sample), the groups were partitioned using the classification criteria of Collins and Read (1990). Securely attached participants = 27%, insecurely attached 73%. An analysis of effect of attachment style on overall pain showed that the Securely Attached group reported less overall pain than the Insecurely Attached group. For Study 2, (using the total clinical sample), the sample comprised 27.3% securely attached and 72.7% insecurely attached participants. The Securely Attached group reported less overall Pain, less Negative Affect and Somatisation than the Insecurely Attached group, and higher levels of Quality of Life. Somatisation provided a significant unique contribution of variance to predicting overall Pain, providing some support for the biopsychosocial model, and Negative Affect (Depression and Anxiety combined) made a significant unique contribution to Quality of Life, explaining 26% of the variance. Gender was unrelated to any variable. For Study 3, the sample consisted of rural and urban participants, and the rural group was significantly older than the urban group. No other differences were found. The groups were combined to form the non-clinical group. The group was evenly divided (50%) between securely and insecurely attached groups. Gender was unrelated to any variable. For the non-clinical group, using the variables investigated in Study 2, there was no difference on overall pain scores, but negative affect and somatisation were higher and quality of life lower in the insecure group than in the secure group. No differences were found on Pain Intensity but Pain Pattern differed between the groups. Three new variables were added to the model - Neuroticism, Function and Disability. Disability and Function were significantly different between the attachment style groups. Age was significantly related to lower pain scores, less loss of function, less disability and higher quality of life. Pain scores were most related to somatisation, with age and quality of life contributing significant variance. Neuroticism added further to this explanation. Negative Affect made the most contribution to the variance explained in quality of life, and neuroticism and function made no significant contribution. Neuroticism and Attachment Style contributed significant amounts of variance to Function. To compare the Secure and Insecure Attachment groups in the Clinical and Non-clinical samples, a matched groups study, N = 190, was conducted. Clinical and non-clinical participants were matched for Age, Gender and Attachment Style. No differences were reported on overall pain between the attachment groups, but differences existed on negative affect, somatisation and quality of life. For sample type, the clinical group reported higher overall pain scores, less negative affect and less somatisation, but no differences were found on quality of life, compared to the non-clinical group. Study 4 was a qualitative study that used structured interviews of 24 clinical and non-clinical participants matched for age, gender, attachment style and etiology. The securely attached group reported having extensive, positive social support, high community involvement and appropriate reliance on medical and allied health care and medications. The insecurely attached group reported more problems with physical pain and psychological distress, less social support, less function and more perceived disability. The insecurely attached group reported more use of medical, allied and alternative health resources. Older securely attached individuals reported the lowest overall pain scores and the highest quality of life. These results support the hypotheses that a secure attachment style contributes to more positive outcomes for individuals with chronic pain syndrome and were consistent with a model of chronic pain that includes biological, psychological and social variables.

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 96-106).

Sleep, emotions and pain are intimately connected, physiologically, by their location and utilization of the same brain centers and neurotransmitters. Sleep disturbances have been clinically observed in chronic pain populations; yet, no treatment program has formally addressed this aspect of patient care. It is hypothesized that a pain population (PN) will differ significantly from a non-injured workforce (WF) when reviewing quantitative and qualitative sleep data. This study strongly supports that sleep disturbances and socioeconomic decrements exist in chronic pain patients. Forty-seven variables were surveyed and 13 were found to show significant differences between the groups and seven were found to discriminate between the PN and WF groups at less than the .0001 level. A discriminant analysis was performed to determine the smallest model which could efficiently classify cases, according to successive root variables. The major discriminators are pain levels, medication, amount of sleep obtained and number of awakenings.

The purpose of the present study was to study the relationship of MCMI-III clinical scales with MMPI-2 clusters in a chronic pain population. Data was obtained through assessment data (N = 242) from the Dallas Spinal Rehabilitation Center (DSRC), that included MMPI-2 and MCMI-III, as well as pre-and post-assessment information (n = 21) and follow-up questionnaires (n = 19). Subjects' age ranged from 18 to 64. Each patient had a primary diagnosis related to a back and/or a cervical injury, a chronic pain diagnosis, and often medical prescription dependency and/or addition. Each has experienced back pain in the lumbar region (L1 to L5) or cervical region (C1 to C7) for an average of 32 months. Patients with thoracic (mid-spine) and carpal tunnel pain were excluded from this study. A multivariate cluster analysis procedure was performed that yielded 3 homogeneous female MMPI-2 clusters and 4 MMPI-2 homogeneous male clusters. Seven multiple regression analyses were performed to determine which MCMI-III clinical scales predicted cluster membership in the MMPI-2 clusters. Results indicated that MCMI-III clinical scales "7" Compulsive, "X" Validity and "C" Borderline were predictors for membership in the male MMPI-2 clusters. Membership in the female MMPI-2 clusters were predicted by MCMI-III clinical scales "4" Histrionic, "T" Drug Dependence and "2A" Avoidant. Nineteen pre-and post-MCMI-IIIs were analyzed for change after participants completed the six-week pain management program. Paired-sample t-tests were performed on these data and revealed that significant change was noted on 10 MCMI-III clinical scales. Follow-up data questionnaires were available on these same individuals. Results from a correlation analysis indicated that patients who reported having supportive relationships with their spouse and family and a secure source of income report better quality of sleep, better mood, are able to relax and are believe that they are able to manage their pain. Participants who were able to relax and remain calm report better quality of sleep, exercise frequently, report better quality of mood and believe that they will return to work soon. Findings from this study suggest that rather than using the MCMI-III as a diagnostic tool, a more efficient use of this instrument would be to understand maladaptive coping styles that may be present under stressful situations. This study's findings suggest that pain treatment program staff could utilize follow up information, as well as diagnostic information about coping strategies that might appear under stress, to shape interventions. Future research might focus on investigation of factors that predict both improvement and program failure, especially those present at initial intake.

This correlational study investigated the relationship between changes in the psychosocial scales of the MPI Screener Patient Report Card (Clark, 1996) with changes in depression and anxiety with a sample of chronic pain patients who completed a 4-week outpatient interdisciplinary treatment program located in a large regional medical center. Race, gender, and primary pain diagnosis were additional predictors. Data analyzed came from an existing patient outcome database (N = 203). Five research assumptions were examined using ten separate (five pre and five post-treatment) hierarchical multiple regression analyses. Statistical significance was found in pre and post-treatment analyses with predictors BDI-II (Beck, Steer, & Brown, 1996) and BAI (Beck & Steer, 1993) on criterions Pain Interference, Emotional Distress, and Life Control, and Total Function.

The financial cost for health care and lost productivity due to chronic pain has been estimated at over $70 billion per year. Researchers have attempted to discover the psychosocial and personality factors that discriminate between people who learn to cope well with chronic pain and those who have difficulty adjusting. The purpose of the present study was to examine the effects of perceived locus of control and dispositional optimism on chronic pain treatment outcomes. Subjects reported significantly lower post-treatment pain levels as compared with pre-treatment levels (M = 0.66, SD = 1.58), t(45) = 2.85, p = .007 (two-tailed), but decreased pain was not associated with scores on the internality dimension of the Pain Locus of Control Scale (PLOC) or on the Life Orientation Test-Revised (LOT-R) (a measure of dispositional optimism). Overall, participants' increased coping ability was associated with scores on the LOT-R, but not with scores on the internality dimension of the PLOC. Subjects with the lowest pre-treatment scores on the LOT-R demonstrated significantly greater increases in post-treatment coping ability than those with the highest scores (F(2,40) = 3.93, p < .03). Participants with the highest pre-treatment scores on both the PLOC internality dimension and the LOT-R demonstrated greater post-treatment coping ability (F(2,32) = 4.65, p < .02), but not less post-treatment pain than other subjects. Participants' post-treatment LOT-R scores were significantly higher than their pre-treatment scores (M = 2.09, SD = 3.96), t(46) = 3.61, p = .001 (two-tailed), but post-treatment PLOC internality scores were not significantly higher than pre-treatment scores. Implications of these results are discussed.