Pain
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Human subjects infected with herpes or varicella-zoster viruses complain of pain, such as allodynia, in or near the region with vesicles. However, the mechanisms of the pain are unclear. We show for the first time that infection with herpes simplex virus type-1 (HSV-1) induces allodynia and hyperalgesia in mice. ⋯ In contrast, when started from days 5 or 6, acyclovir treatment slightly inhibited the development of skin lesions and the viral proliferation, but not allodynia and hyperalgesia. These results suggest that the propagation of HSV-1 in the dorsal root ganglia produces allodynia and hyperalgesia as a result of functional abnormality of the sensory neurons in mice. This may be a useful model for studying the mechanisms of herpetic pain.
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Neuropathic pain is often associated with the appearance of pain in regions not related to the injured nerve. One mechanism that may underlie neuropathic pain is abnormal, spontaneous afferent drive which may contribute to NMDA-mediated central sensitization by the actions of glutamate and by the non-opioid actions of spinal dynorphin. In the present study, injuries to lumbar or sacral spinal nerves elicited elevation in spinal dynorphin content which correlated temporally and spatially with signs of neuropathic pain. ⋯ Spinal injection of antiserum to dynorphin A((1-17)) and of MK-801 both blocked thermal hyperalgesia, but not tactile allodynia, of the hindpaw after S(2) ligation. These data suggest that the elevated spinal dynorphin content consequent to peripheral nerve injury may drive sensitization of the spinal cord, in part through dynorphin acting directly or indirectly on the NMDA receptor complex. Furthermore, extrasegmental increases in spinal dynorphin content may partly underlie the development of extraterritorial neuropathic pain.
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The anti-nociceptive and locomotor effects of the nicotinic acetylcholine receptor (nAChR) agonists (+)-epibatidine and ABT-594 were compared in the rat. Acute thermal nociception was measured using the tail flick test. Mechanical hyperalgesia was measured as paw withdrawal threshold (PWT) in response to a mechanical stimulus in two animal models of persistent pain; (1) 24 h following subplantar injections of Freund's complete adjuvant (FCA) into the left hind paw or (2) 11-15 days following a partial ligation of the left sciatic nerve. ⋯ In summary, ABT-594 is less potent than (+)-epibatidine in assays of acute and persistent pain and in the rotarod assay. However, ABT-594 displayed a clearer separation between its motor and anti-hyperalgesic effects. This shows that nicotinic agonists with improved selectivity between the nicotinic receptor subtypes could provide strong analgesic effects with a much improved therapeutic window.
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Meta Analysis
Teasing apart quality and validity in systematic reviews: an example from acupuncture trials in chronic neck and back pain.
The objectives of the study were (1) to carry out a systematic review to assess the analgesic efficacy and the adverse effects of acupuncture compared with placebo for back and neck pain and (2) to develop a new tool, the Oxford Pain Validity Scale (OPVS), to measure validity of findings from randomized controlled trials (RCTs), and to enable ranking of trial findings according to validity within qualitative reviews. Published RCTs (of acupuncture at both traditional and non-traditional points) were identified from systematic searching of bibliographic databases (e.g. MEDLINE) and reference lists of retrieved reports. ⋯ OPVS is a useful tool for assessing the validity of trials in qualitative reviews. With acupuncture for chronic back and neck pain, we found that the most valid trials tended to be negative. There is no convincing evidence for the analgesic efficacy of acupuncture for back or neck pain.
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Randomized Controlled Trial Clinical Trial
Spatial mapping of the zone of secondary hyperalgesia reveals a gradual decline of pain with distance but sharp borders.
The purpose of this study was to examine how pain to punctate mechanical stimuli varies with position within the zone of secondary hyperalgesia. Secondary hyperalgesia was produced by an intradermal injection of capsaicin (50 microg) into the volar forearm of human volunteers (n=9). Before and at 20, 60 and 100 min after the capsaicin injection, a computer-controlled electromechanical stimulator was used to deliver controlled-force stimuli to the skin via a 12-mm wide, 100-microm thick blade probe. ⋯ This finding unlikely reflects a ceiling effect because pain ratings within the zone of secondary hyperalgesia increased linearly with force. The relatively uniform pain ratings to the blade stimuli within the zone of secondary hyperalgesia and the sharp border that delimits the zone of hyperalgesia indicate that this sensory disturbance approaches being an 'all-or-nothing' phenomenon. Thus, a two-state model for central plasticity is needed to explain secondary hyperalgesia.