Pain
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Peripheral nerve injury provokes heightened excitability of primary sensory afferents including nociceptors, and elicits ectopic activity in lesioned and neighboring intact nerve fibers. The major transmitter released by sensory afferents in the superficial dorsal horn of the spinal cord is glutamate. Glutamate is critically involved in nociceptive signaling and the development of neuropathic pain. ⋯ Treatment with the β-lactam antibiotic ceftriaxone increased the expression of glutamate transporter 1 (Glt1) in the dorsal horn after SNI, raised transmitter uptake, and lowered extracellular glutamate. Improving glutamate clearance prevented the facilitation of transmitter release by mGluR5 and attenuated neuropathic pain-like behavior. Balancing glutamate release and uptake after nerve injury should be an important target in the management of chronic neuropathic pain.
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A critical component in development of opioid analgesics is assessment of their abuse liability (AL). Standardization of approaches and measures used in assessing AL have the potential to facilitate comparisons across studies, research laboratories, and drugs. The goal of this report is to provide consensus recommendations regarding core outcome measures for assessing the abuse potential of opioid medications in humans in a controlled laboratory setting. ⋯ A brief historical perspective on AL testing is provided, and those measures that can be considered primary and secondary outcomes and possible additional outcomes in AL assessment are then discussed. These outcome measures include the following: subjective effects (some of which comprise the primary outcome measures, including drug liking; physiological responses; drug self-administration behavior; and cognitive and psychomotor performance. Before presenting recommendations for standardized approaches and measures to be used in AL assessments, the appropriateness of using these measures in clinical trials with patients in pain is discussed.
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Slow-release strong opioids (SRSO) are indicated in patients with severe chronic pain. Side effects, lack of efficacy and risk of dependency limit their use in clinical practice. The aim of this study was to explore prescription patterns of SRSO in Swedish real-world data on patients with a diagnosis related to chronic pain (DRCP). ⋯ In conclusion, fewer patients remain on SRSO in the long-term in clinical practice than reported in previous clinical trials. Oxycodone is the most common first SRSO prescription and one-third of patients get a prescription indicating psychiatric comorbidity. Our interpretation of these findings are that there is need for better treatment options for these patients, and that more effort is needed to improve treatment guidelines and to ascertain that these guidelines are followed.
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A connection between pain and depression has long been recognized in the clinical setting; however, its mechanism remains unclear. This study showed that mechanical hyperalgesia induced by unilateral temporomandibular joint (TMJ) inflammation was exacerbated in Wistar-Kyoto (WKY) rats with genetically predisposed depressive behavior. Reciprocally, TMJ inflammation enhanced depressive behavior such that a lower nociceptive threshold correlated with a higher score of depressive behavior in the same WKY rats. ⋯ Intracisternal administration of 6-chloromelatonin (250 μg, twice daily for 7 days) concurrently attenuated mechanical hyperalgesia and depressive behavior in WKY rats as well as downregulated the NR1 expression in the ipsilateral Sp5C. In patch-clamp recordings, melatonin dose-dependently decreased NMDA-induced currents in spinal cord dorsal horn substantia gelatinosa neurons. These results demonstrate a reciprocal relationship between TMJ inflammation-induced mechanical hyperalgesia and depressive behavior and suggest that the central melatoninergic system, through modulation of the NMDA receptor expression and activity, may play a role in the mechanisms of the comorbidity between pain and depression.
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Whether self-reported lifetime civilian and war-related potential traumatic events are associated with widespread pain (WP) and if so, whether the association is attributable to posttraumatic stress disorder (PTSD) and depression has not been studied in a representative sample of the general population. In a randomly selected sample of the German general population, persons aged 60-85 years answered validated self-rating instruments: Regional Pain Scale, trauma list of the Composite International Diagnostic Interview, Posttraumatic Diagnostic Scale, and Patient Health Questionnaire 2. Participants with WP were compared with participants with no or local or regional pain (controls). ⋯ The significant association between some potential traumatic events and WP was completely abrogated after adjusting for demographic variables and PTSD. In the final model, PTSD (odds ratio 3.43, 95% confidence interval 1.88-6.26) and lifetime employment status as a worker (odds ratio 1.55, 95% confidence interval 1.04-2.31) predicted WP. Prospective studies are necessary to understand the temporal association of PTSD and WP.