Articles: hyperalgesia.
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Opioids are powerful analgesics when used to treat acute pain and some forms of chronic pain. In addition, opioids can preempt some forms of central sensitization. Here we review evidence that opioids may also induce and perhaps reverse some forms of central sensitization.
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J. Pharmacol. Exp. Ther. · Apr 2005
AMG 9810 [(E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)acrylamide], a novel vanilloid receptor 1 (TRPV1) antagonist with antihyperalgesic properties.
The vanilloid receptor 1 (VR1 or TRPV1) is a membrane-bound, nonselective cation channel expressed by peripheral sensory neurons. TRPV1 antagonists produce antihyperalgesic effects in animal models of inflammatory and neuropathic pain. Here, we describe the in vitro and in vivo pharmacology of a novel TRPV1 antagonist, AMG 9810, (E)-3-(4-t-butylphenyl)-N-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)acrylamide. ⋯ In vivo, AMG 9810 is effective at preventing capsaicin-induced eye wiping in a dose-dependent manner, and it reverses thermal and mechanical hyperalgesia in a model of inflammatory pain induced by intraplantar injection of complete Freund's adjuvant. At effective doses, AMG 9810 did not show any significant effects on motor function, as measured by open field locomotor activity and motor coordination tests. AMG 9810 is the first cinnamide TRPV1 antagonist reported to block capsaicin-induced eye wiping behavior and reverse hyperalgesia in an animal model of inflammatory pain.
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The Journal of physiology · Apr 2005
Comparative StudyMuscular mechanical hyperalgesia revealed by behavioural pain test and c-Fos expression in the spinal dorsal horn after eccentric contraction in rats.
Delayed onset muscle soreness (DOMS) is quite common, but the mechanism for this phenomenon is still not understood; even the existence of muscle tenderness (mechanical hyperalgesia) has not been demonstrated in experimental models. We developed an animal model of DOMS by inducing eccentric contraction (lengthening contraction, ECC) to the extensor digitorum longus muscle (EDL), and investigated the existence of mechanical hyperalgesia in the EDL by means of behavioural pain tests (Randall-Selitto test and von Frey hair test, applied to/through the skin on the EDL muscle) and c-Fos expression in the spinal dorsal horn. We found that the mechanical withdrawal threshold measured with the Randall-Selitto apparatus decreased significantly between 1 and 3 days after ECC, while that measured by von Frey hairs did not. ⋯ This increase was observed in the superficial dorsal horn of the L4 segment of the ipsilateral side, and was clearly suppressed by morphine treatment (10 mg kg(-1), i.p.). These results demonstrated the existence of mechanical hyperalgesia in the muscle subjected to ECC. This model could be used for future study of the neural mechanism of muscle soreness.
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The management of chronic pain represents a significant public health issue in the United States. It is both costly to our health care system and devastating to the patient's quality of life. The need to improve pain outcomes is reflected by the congressional declaration of the present decade as the "Decade of Pain Control and Research," and the acknowledgment in January 2001 of pain as the "fifth vital sign" by the Joint Commission of Healthcare Organizations. ⋯ The rapidly evolving symptom- and mechanism-based approach to the treatment of neuropathic pain holds promise for improving the quality of life of our patients with neuropathic pain.
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Clinical Trial Controlled Clinical Trial
Widespread sensory hypersensitivity is a feature of chronic whiplash-associated disorder but not chronic idiopathic neck pain.
To investigate sensory changes present in patients with chronic whiplash-associated disorders and chronic idiopathic neck pain using a variety of quantitative sensory tests to better understand the pain processing mechanisms underlying persistent symptoms. ⋯ Both chronic whiplash-associated disorders and idiopathic neck pain groups were characterized by mechanical hyperalgesia over the cervical spine. Whiplash subjects showed additional widespread hypersensitivity to mechanical pressure and thermal stimuli, which was independent of state anxiety and may represent changes in central pain processing mechanisms. This may have implications for future treatment approaches.