The journal of pain : official journal of the American Pain Society
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The experience of unpredictable pain fluctuations can trigger anticipatory pain-related fear. When discrete predictors for pain are lacking, fear typically accrues to the broader environmental context: a phenomenon referred to as contextual pain-related fear. We examined whether conceptual similarity between discrete contexts facilitates pain-related fear generalization; this mechanism is known as category-level fear generalization. ⋯ We measured self-reported pain-related fear, expectancy, and eyeblink startle. Results indicated higher pain-related fear reports, but no elevated startle responses, for generalization contexts that were trained to be similar to the original unpredictable context rather than the predictable pain context. This highlights a potential pathway through which neutral contexts can elicit pain-related fear and motivate avoidance behavior associated with chronic pain disability.
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Women have a higher prevalence of chronic noncancer pain conditions and report more severe pain, yet, it is not known if the association between long-term opioid analgesic use (OAU) and risk of a new depression episode (NDE) differs according to gender. We analyzed patient data from the Veterans Health Administration (VHA; 2000-2012; n = 70,997) and a large private-sector health care organization (2003-2012; n = 22,981) to determine whether long-term OAU and risk of NDE differed according to gender. Patients were free of depression and OAU for 2 years before baseline. ⋯ In private sector patients, there was no gender difference in the association between more than 90-day OAU and NDE (female HR = 1.97 [95% CI, 1.64-2.37] vs male HR = 1.99 [95% CI, 1.44-2.74]). Risk of NDE after long-term OAU is similar in men and women in private sector patients but may differ for VHA patients. Future prospective studies are needed to identify mechanisms for the association between longer OAU and NDE.
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Providers are being asked to decrease the emphasis and overutilization of long-term opioid therapy, but many are left without proper guidance on appropriate utilization of nonopioid therapies. Furthermore, therapeutic options are quite limited and many providers lack confidence in distinguishing available alternatives. When first-line therapy has failed in a patient, there is an apparent lack of knowledge on how to proceed with choosing subsequent therapy. ⋯ Sodium channel blocker doses used in certain pain syndromes are outlined with a call for further research to better understand their place in chronic pain management. Identification of sodium channel subtypes with links to specific pain conditions and the ability to target them hints at the potential for truly individualized therapy. Sodium channel inhibitors are underutilized on the basis of available evidence, and emerging research has identified this area as promising for additional clinical trials to better guide clinical practice.
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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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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.