Pain
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Attitudes to pain medication are important aspects of adjustment to chronic pain. They are measured by the 47-item Pain Medication Attitudes Questionnaire (PMAQ). To measure those attitudes more quickly and easily, we developed and evaluated a 14-item PMAQ using data from 3 separate surveys of people with pain in the general population. ⋯ Confirmatory factor analysis showed that the 14-item PMAQ retained the 7-factor structure of the 47-item version, and correlations with other measures showed that it retained the validity of the 47-item version. The PMAQ scale Need was the most significant independent predictor of analgesic dependence in each of 4 separate multiple regression analyses. This short form of the PMAQ allows attitudes to pain medications to be measured in a valid and more efficient way.
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Drugs able to treat both nociceptive and neuropathic pain effectively without major side effects are lacking. We developed a bifunctional peptide-based hybrid (KGNOP1) that structurally combines a mu-opioid receptor agonist (KGOP1) with antinociceptive activity and a weak nociceptin receptor antagonist (KGNOP3) with anti-neuropathic pain activity. We investigated KGNOP1-related behavioral effects after intravenous administration in rats by assessing thermal nociception, cold hyperalgesia in a model of neuropathic pain induced by chronic constriction injury of the sciatic nerve, and plethysmography parameters including inspiratory time (TI) and minute ventilation (VM) in comparison to the well-known opioid analgesics, tramadol and morphine. ⋯ KGNOP1 and KGOP1 produced a larger increase in TI and deleterious decrease in VM in comparison to morphine and tramadol (ED50(TI): 0.63, 0.52, 12.2, and 50.9 μmol/kg; ED50(VM): 0.57, 0.66, 10.6, and 50.0 μmol/kg, respectively). Interestingly, the calculated ratios of anti-neuropathic pain/antinociceptive to respiratory effects revealed that KGNOP1 was safer than tramadol (ED50 ratio: 5.44 × 10 vs 0.24) and morphine (ED50 ratio: 0.72 vs 1.39). We conclude that KGNOP1 is able to treat both experimental neuropathic and nociceptive pain, more efficiently and safely than tramadol and morphine, respectively, and thus should be a candidate for future clinical developments.
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Chronic pain conditions are often comorbid with alcohol abuse. "Self-medication" with alcohol introduces a host of problems associated with the abuse of alcohol which over time has the potential of exacerbating the painful condition. Despite the prevalence of chronic pain being associated with alcohol abuse, rodent models which mimic the comorbid conditions are lacking. In this study, we model osteoarthritis (OA) in C57BL/6J mice by surgically destabilizing the medial meniscus (DMM). ⋯ Compared with sham controls, DMM mice consumed more EtOH and preferred EtOH over water at the 20% EtOH concentration. Histological analysis verified that the DMM mice exhibited significant damage to the articular cartilage and osteophyte growth compared with sham controls and these measures of the severity of OA correlated with the amount of ethanol intake. Thus, the combination of the DMM model of OA with the enhanced two-bottle ethanol choice is a potential preclinical approach in mice by which the basis of the comorbid association of alcohol abuse and chronic pain conditions can be explored.
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Randomized Controlled Trial Multicenter Study
Psychosocial factors predict opioid analgesia via endogenous opioid function.
Use of opioid analgesics for management of chronic nonmalignant pain has become common, yet there are presently no well-validated predictors of optimal opioid analgesic efficacy. We examined whether psychosocial factors (eg, depressive symptoms) predicted changes in spontaneous low back pain after administration of opioid analgesics, and whether endogenous opioid (EO) function mediated these relationships. Participants with chronic low back pain but who were not chronic opioid users (N = 89) underwent assessment of low back pain intensity pre- and post-drug in 3 (counterbalanced) conditions: (1) placebo, (2) intravenous naloxone, and (3) intravenous morphine. ⋯ Bootstrapped mediation analyses showed that links between morphine analgesic responses and depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability were partially mediated by EO function. Results suggest that psychosocial factors predict elevated analgesic responses to opioid-based medications, and may serve as markers to identify individuals who benefit most from opioid therapy. Results also suggest that people with greater depressive symptoms, trait anxiety, pain catastrophizing, and perceived disability may have deficits in EO function, which may predict enhanced response to opioid analgesics.
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Randomized Controlled Trial
Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: A randomized, blinded trial.
Perioperative handling of surgical patients with opioid dependency represents an important clinical problem. Animal studies suggest that ketamine attenuates central sensitization and hyperalgesia and thereby reduces postoperative opioid tolerance. We hypothesized that intraoperative ketamine would reduce immediate postoperative opioid consumption compared with placebo in chronic pain patients with opioid dependency undergoing lumbar spinal fusion surgery. ⋯ Back pain at 6 months postoperatively compared with preoperative pain was significantly more improved in the ketamine group compared with the placebo group, P = 0.005. In conclusion, intraoperative ketamine significantly reduced morphine consumption 0 to 24 hours after lumbar fusion surgery in opioid-dependent patients. The trend regarding less persistent pain 6 months postoperatively needs further investigation.