The journal of pain : official journal of the American Pain Society
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Comparative Study
Novel Endomorphin Analogs are More Potent and Longer Lasting Analgesics in Neuropathic, Postoperative, Inflammatory, and Visceral Pain Relative to Morphine.
Activation of the mu-opioid receptor provides the gold standard for pain relief, but most opioids used clinically have adverse effects that have contributed to an epidemic of overdose deaths. We recently characterized mu-opioid receptor selective endomorphin (EM) analogs that provide potent antinociception with reduction or absence of a number of side effects of traditionally prescribed opioids including abuse liability, respiratory depression, motor impairment, tolerance, and inflammation. The current study explores the effectiveness of these EM analogs relative to morphine in four major pain models by intrathecal as well as intravenous administration in male Sprague Dawley rats and subcutaneous administration in male CD-1 mice. In the spared nerve injury model of neuropathic pain, mechanical allodynia and mechanical hyperalgesia were assessed with von Frey and Randall-Selitto tests, respectively. In the paw incision model of postoperative pain, von Frey testing was used to assess mechanical allodynia and thermal hyperalgesia was evaluated with Hargreaves testing. In the Complete Freund's Adjuvant model of inflammatory pain, thermal hyperalgesia was assessed using Hargreaves testing. In CD-1 mice, visceral pain was assessed with the acetic acid writhing test. In all cases, EM analogs had equal or greater potency and longer duration of action relative to morphine. The data suggest that EM analogs, particularly analog 4 (ZH853), could provide effective therapy for a diverse spectrum of pain conditions with low risk of adverse side effects compared with currently used opioids such as morphine. ⋯ Novel EM analogs show equal or greater potency and effectiveness relative to morphine in multiple pain models. Together with substantially reduced side effects, including abuse liability, the compounds show promise for addressing the critical need for effective pain relief as well as reducing the opioid overdose epidemic.
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An age-related decline in endogenous pain inhibitory processes likely places older adults at an increased risk for chronic pain. Limited research indicates that older adults may be characterized by deficient offset analgesia, an inhibitory temporal sharpening mechanism that increases the detectability of minor decreases in noxious stimulus intensity. The primary purpose of the study was to examine age differences in offset analgesia in community-dwelling younger, middle-aged, and older adults. ⋯ The results indicated that older and middle-aged adults showed reduced offset analgesia compared with younger adults in the 1.0°C and .4°C offset trials. Furthermore, the magnitude of offset analgesia predicted self-reported bodily pain, with those exhibiting reduced offset analgesia reporting greater bodily pain. Dysfunction of this endogenous inhibitory system could increase the risk of developing chronic pain for middle-aged and older adults.
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Randomized Controlled Trial
The Effect of Preoperative Intra-Articular Methylprednisolone on Pain after TKA: a Randomized Double-Blinded Placebo Controlled Trial in Patients with High-Pain Knee Osteoarthritis and Sensitization.
In a randomized, double-blind, placebo controlled trial, we investigated the postoperative analgesic effect of a single intra-articular injection of 40 mg methylprednisolone acetate (MP) administered 1 week before total knee arthroplasty (TKA). Forty-eight patients with high pain osteoarthritis (≥5 on a numeric rating scale during walk) and sensitization (pressure pain threshold <250 kPa), aged 50 to 80 years and scheduled for primary unilateral TKA under spinal anaesthesia were included. ⋯ No difference in the proportion of patients with moderate/severe pain was found between MP/placebo groups at 24 hours (67% and 74%, χ2 = .2, P = .63, odds ratio = .7, 95% confidence interval = .2-2.8) or at 48 hours (57% and 68%, χ2 = .5, P = .46, odds ratio = .6, 95% confidence interval = .2-2.3), and no difference between groups in postoperative sensitization was found (P > .4) despite reduced preoperative intra-articular inflammation (IL-6) in the MP group versus placebo (median change in IL-6 = -70 pg/mL, interquartile range = -466 to 0 vs. 32 pg/mL, interquartile range = -26 to 75, P = .029). Alternative central or peripheral analgesic interventions in this high-risk group are required.
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Researchers have identified trajectories of pain derived using statistical techniques on longitudinal data. These trajectories have potential to be of use clinically but the repeated data collection required is currently impractical for such situations. Our aim was to investigate the validity of a self-report (Visual Trajectories Questionnaire-Pain) for pain. ⋯ As expected variables such as pain intensity and widespreadness, other symptoms, and psychological distress showed an increasing trend of severity across trajectory categories in line with the hypothesized model. In conclusion, the self-report single-item Visual Trajectories Questionnaire-Pain is acceptable to patients and supported by evidence of face, criterion, and construct validity. Further research is needed to investigate the clinical usefulness of the question.
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Chronic pain is a common condition associated with psychological distress, functional impairments, and age-associated comorbidity. Preliminary studies, on the basis of relatively small sample sizes, suggest that the combination of chronic pain and stress is associated with telomere shortening, a widely recognized marker of cellular aging. We sought to determine the cross-sectional association of chronic pain with telomere length in 7,816 community-dwelling adults ages 20 years and older who participated in the 1999 to 2002 National Health and Nutrition Examination Survey. ⋯ The age-adjusted means (standard error) of telomere length telomere to single copy gene ratios were 1.04 (.02), 1.03 (.02), and 1.02 (.02) in participants with no chronic pain, chronic regional pain, and chronic widespread pain, respectively (P = .69). In addition, chronic pain did not modify the effects of age, sex, race/ethnicity, education, or psychological distress on telomere length. In summary, chronic regional and widespread pain were not associated with telomere length in this nationally representative study; however, we could not determine associations of pain duration and severity with telomere length because of limitations in pain assessment data.