Jinrun Gao

Do Opioids Induce Hyperalgesia in Humans? An Evidence-Based Structured Review

UNLABELLED DESIGN/OBJECTIVES: Consistent rodent evidence indicates that opioid exposure will decrease the rodents pain threshold (ptr). This is termed opioids-induced hyperalgesia (OIH). Currently, the consistency of the evidence for the occurrence of OIH in humans is unclear. This is a structured evidence-based review for all levels of evidence (all studies and case reports) on OIH in humans in order to determine the consistency of this evidence. METHODS Computer and manual literature searches yielded 504 OIH references (human and animal). Of these, 48 remained after application of inclusion/exclusion criteria. These references addressed 10 hypotheses that the OIH literature has utilized to test for the possibility of OIH in humans. These are the following: opioid addicts maintained on opioids will have decreased ptr and/or tolerance; detoxifying opioid addicts from opioids will increase their ptr and/or tolerance; stopping, decreasing, or rotating to a different opioid or detoxifying from an opioid will improve pain and/or allodynia; chronic pain patients(CPPs) placed on opioids will develop decreased ptr and/or tolerance; CPPs on opioids will have decreased ptr and/or tolerance vs CPPs not on opioids; opioid infusion in normal volunteers or CPPs will decrease ptr and/or tolerance; former opioid addicts exposed to opioids will demonstrate a decrease in ptr and/or tolerance; opioid infusion in normal volunteers will increase secondary hyperalgesia as measured by allodynia or hyperalgesia; perioperative opioids will increase postoperative pain and/or opioid requirements; and placement on opioids postsurgery leads to progressive increased intake (acute tolerance). Each report was characterized by the type of study it represented according to the Agency for Health Care Policy and Research (AHCPR) guidelines and independently rated by two raters according to 14 quality criteria with a quality score calculated. For studies under each hypothesis, an average quality score and the percentage of studies supporting the hypothesis was calculated. Finally, for studies under each hypothesis, utilizing AHCPR criteria, a consistency rating was derived based on the percentage score of studies supporting the hypothesis. RESULTS Two studies had quality scores below 65% and were not utilized. Overall, the strongest evidence (consistent, A) came from opioid infusion studies in normal volunteers as measured by secondary hyperalgesia. This evidence was supported by inconsistent evidence (C) from: studies addressing opioid infusions in normal volunteers or CPPs for decreasing ptr and/or tolerance; and studies addressing increases in postop opioid requirements or pain if peri-opioids were utilized. For the other seven hypotheses, there were too few studies to draw a conclusion or the evidence for the hypothesis were case reports or the results of the studies within the hypothesis were not interpretable. CONCLUSIONS There is not sufficient evidence to support or refute the existence of OIH in humans except in the case of normal volunteers receiving opioid infusions. Prospective CPP clinical studies measuring ptrs and tolerances pre- and post-opioid placement with CPP non-opioid control groups are required.

Is chronic pain associated with somatization/hypochondriasis? An evidence-based structured review.

Study Design:  This is an evidence‐based structured review.

What is the evidence for chronic pain being etiologically associated with the DSM-IV category of sleep disorder due to a general medical condition? A structured evidence-based review.

DESIGN This is a structured evidence-based review of all available studies on the relationship between chronic pain and sleep problems as defined by the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV) category of sleep disorder due to a general medical condition. OBJECTIVES To determine whether chronic pain is etiologically associated with this sleep category. METHODS Computer and manual literature searches yielded 146 references that addressed this area of study. One hundred and five studies were excluded from detailed review based on exclusion criteria detailed by this category of sleep disorders. Forty-one studies were reviewed in detail and sorted according to six natural groupings: multivariate analysis, prospective studies, path analysis, correlation between pain and sleep problems, univariate analysis using comparison groups, and do nonsedating drugs with analgesic properties improve sleep? Study characteristics were abstracted into tabular form and each report was characterized by the type of study it represented according to the Agency for Health Care Policy and Research (AHCPR) guidelines. Each study was independently evaluated by two raters according to 12 quality criteria and an independent quality score was calculated. Studies were not utilized in the calculations unless their quality score (utilizing both raters) was greater than 60%. For each of the above groupings, an average quality score was calculated and a calculation performed as to the percentage of studies that supported the hypothesis that pain is etiologically related to the above DSM-IV category of sleep disorders. Finally, the strength and consistency of the evidence for this hypothesis was rated according to the AHCPR guidelines. RESULTS Of the 41 reports, all had quality scores greater than 60%. In all the above groupings except for multivariate analysis, 100% of the studies supported this hypothesis. In the multivariate analysis grouping, 77.2% of the studies supported this hypothesis. The strength and consistency of this evidence was rated at A (highest possible) for all study groupings except multivariate (B rating) and path analysis where there were too few studies to generate a conclusion. For all the studies combined, 89.7% of the studies supported this hypothesis. This evidence was rated as A: consistent, multiple studies. CONCLUSIONS The results of this evidence-based structured review indicate that for the pain-sleep studies defined by the DSM-IV category of sleep disorder due to a general medical condition,chronic pain may be etiologically related to that sleep problem. However, these results do not preclude this relationship from being bidirectional.

The Pain Suicidality Association: A Narrative Review

OBJECTIVES The objective of this narrative review was to examine recent evidence and, when necessary, past evidence on the association between pain and suicidality. DESIGN Fifty-eight research reports were found on this topic, which had not previously been reviewed. These reports were divided into groups by whether they addressed suicide ideation (SI), suicide attempts (SAs), or suicide completion (SC), and what population they represented (acute pain patients [APPs], chronic pain patients [CPPs], other than APPs/CPPs) and whether they controlled for relevant confounders. Information as to whether the results of these studies supported/did not support the association of pain and suicidality was abstracted. For each group of studies (above), a vote counting method was utilized to determine the overall percentage of studies supporting/not supporting the association of pain and suicidality. According to this percentage, the consistency of the data supporting this association was rated according to Agency for Healthcare Research and Quality guidelines. RESULTS The following groups of studies received an A consistency rating (consistent evidence from multiple studies): SI, SA, and SC for other than APPs/CPPs; and SI, SA, and SC for CPP prevalence greater than an appropriate control group. Also, a subgroup of the SI, SA, and SC studies for other than APPs/CPPs had controlled for behavioral issues (potential confounders). These three subgroups also received an A consistency rating. The 58 studies also identified a number of new predictor variables for SI, SA, and SC in CPPs. CONCLUSIONS These studies solidify the evidence for an association between pain and SI, SA, and SC in both CPPs and other than APPs/CPPs.

What Is the Evidence that Neuropathic Pain Is Present in Chronic Low Back Pain and Soft Tissue Syndromes? An Evidence‐Based Structured Review

OBJECTIVES The objectives of this evidence-based review were to review the evidence for whether neuropathic pain (NP) is associated with chronic low back pain (CLBP) and soft tissue syndromes (STS), and review the reported prevalence percentages for NP within these syndromes. METHODS Of 816 reports, 11 addressed the diagnosis of NP in CLBP and five of NP in STS. Studies were grouped by the method of arrival at an NP diagnosis, e.g., physical examination, type of NP inventory utilized, etc. The reported prevalence of NP was determined by aggregating all the patients in all the studies in each grouping. Similarly, the reported prevalence of NP within CLBP and STS was determined by aggregating all the patients with NP from all the studies in those groups. Each study was independently rated by two raters according to 11 quality criteria generating a quality score. The strength and consistency (SAC) of the evidence represented by each grouping was rated according to Agency for Health Care Policy and Research guidelines. RESULTS In each grouping, 100% of the studies reported some prevalence of NP (none reported zero prevalence). Aggregated NP prevalence for CLBP was 36.6% (SAC level A [consistent multiple studies]) and for STS 41.1% (SAC level A). There was significant variation in prevalence according to the method utilized to diagnose NP. CONCLUSION There is consistent evidence by all methods that NP is present in CLBP and STS. Reported prevalence percentages by all methods are substantial. This has significant implications for the treatment of CLBP and STS.

Chronic Pain Types Differ in Their Reported Prevalence of Post -Traumatic Stress Disorder (PTSD) and There Is Consistent Evidence That Chronic Pain Is Associated with PTSD: An Evidence-Based Structured Systematic Review

Objectives The hypotheses of this systematic review were the following: 1) Prevalence of post-traumatic stress disorder (PTSD) will differ between various types of chronic pain (CP), and 2) there will be consistent evidence that CP is associated with PTSD. Methods Of 477 studies, 40 fulfilled the inclusion/exclusion criteria of this review and were grouped according to the type of CP. The reported prevalence of PTSD for each grouping was determined by aggregating all the patients in all the studies in that group. Additionally all patients in all groupings were combined. Percentage of studies that had found an association between CP and PTSD was determined. The consistency of the evidence represented by the percentage of studies finding an association was rated according to the Agency for Health Care Policy and Research guidelines. Results Grouping PTSD prevalence differed ranging from a low of 0.69% for chronic low back pain to a high of 50.1% in veterans. Prevalence in the general population with CP was 9.8%. Of 19 studies, 16 had found an association between CP and PTSD (84.2%) generating an A consistency rating (consistent multiple studies). Three of the groupings had an A or B (generally consistent) rating. The veterans grouping received a C (finding inconsistent) rating. Conclusion The results of this systematic review confirmed the hypotheses of this review.

Are Chronic Low Back Pain Patients Who Smoke at Greater Risk for Suicide Ideation

OBJECTIVES There is significant psychiatric literature indicating that smoking is associated with all forms of suicidality, including suicide ideation. The goal of this study was to determine if smoking is associated with suicide ideation in chronic low back pain (CLBP) patients. DESIGN CLBP patients identified themselves as either current smokers (N = 81) or nonsmokers (N = 140) and completed a number of evaluation instruments, which included the Beck Depression Inventory (BDI) and the Coping Strategies Questionnaire (CSQ). BDI question number 9 was utilized to define CLBP with suicide ideation and subsequently, in addition, items number 3 and number 6 from the CSQ were added to the BDI item number 9 in order to fully capture CLBP with suicide ideation. Utilizing this expanded definition of suicide ideation (BDI plus CSQ), CLBP smokers were compared with CLBP nonsmokers for the frequency of suicide ideation. Regression analysis was utilized to investigate the CLBP smoking suicide ideation group. Finally, we investigated whether heavy use of alcohol and coffee impacted on CLBP heavy smokers in terms of increasing suicide ideation risk. SETTING CLBP patients were recruited from a pain facility. RESULTS CLBP smokers were more likely to complain of suicide ideation, and this relationship correlated with the number of cigarettes smoked per day. Seventy-eight percent of the CLBP smokers were classified correctly in terms of the presence of suicide ideation by three variables: diagnosis of major depression, Function Assessment Questionnaire total score, and BDI total score. The relative risk of suicide ideation was increased by combining heavy smoking (greater than one pack per day) with heavy alcohol use. CONCLUSIONS CLBP smokers appear to be at greater risk for suicide ideation than nonsmoking CLBP patients. The risk of suicide ideation is even greater if the CLBP patient is a heavy smoker and has problems with alcohol.

Variables Associated with Self‐Prediction of Psychopharmacological Treatment Adherence in Acute and Chronic Pain Patients

Objectives:  The objectives of this article were the following: (1) determine risk for self‐predicted future psychopharmacological nonadherence in rehabilitation acute pain patients (APPs) and rehabilitation chronic pain patients (CPPs) vs. pain‐free community controls and community patients, and (2) determine which variables predict nonadherence.

Prevalence comparisons of somatic and psychiatric symptoms between community nonpatients without pain, acute pain patients, and chronic pain patients

OBJECTIVES Somatic/psychiatric symptoms are frequently found in chronic pain patients (CPPs). The objectives of this study were to determine 1) which somatic/psychiatric symptoms are more commonly found in acute pain patients (APPs) and CPPs vs community nonpatients without pain (CNPWPs) and 2) if somatic/psychiatric symptom prevalence differs between APPs and CPPs. DESIGN The above groups were compared statistically for endorsement of 15 symptoms: fatigue, numbness/tingling, dizziness, difficulty opening/closing mouth, muscle weakness, difficulty staying asleep, depression, muscle tightness, nervousness, irritability, memory, falling, nausea, concentration, and headaches. RESULTS After controlling for age, gender, and level of pain, APPs and CPPs had a statistically significantly greater prevalence (at a P < 0.01 level) for 11 and 13 symptoms, respectively, vs CNPWPs. After controlling for age, gender, and level of pain, CPPs had a statistically significantly greater prevalence (at a P < 0.01 level) for eight symptoms vs APPs. Symptoms were highly correlated in both APPs and CPPs. CONCLUSIONS CPPs are characterized to a significantly greater extent than comparison groups by somatic/psychiatric symptoms that are highly intercorrelated. This has implications for clinical practice and future research.

Exploration of Anger Constructs in Acute and Chronic Pain Patients vs. Community Patients

Objectives:  (1) Determine and compare prevalence of forms of anger (FOA; anger, hostility, aggression, anger‐in, anger‐out, chronic anger) in community nonpatients (n = 478), community patients (n = 158), acute pain patients (APPs; n = 326), chronic pain patients (CPPs; n = 341); and (2) develop FOA predictor models in APPs and CPPs.