Articles: hyperalgesia.
-
Comparative Study
Synergy between intrathecal omega-conotoxin CVID and dexmedetomidine to attenuate mechanical hypersensitivity in the rat.
The analgesic effects of intrathecal (i.t.) omega-conotoxin CVID, an N-type Ca2+ channel antagonist, and the alpha2-adrenoceptor agonist, dexmedetomidine, were tested alone and in combination following unilateral ligation of L (lumbar) 5/6 spinal nerves in rats. Mechanical allodynia was observed prior to insertion of an i.t. catheter. Effects and interactions of omega-conotoxin CVID (0.01-10 microg/kg) and dexmedetomidine (0.1-10 microg/kg) were tested on allodynic and tail flick (thermal stimulus) responses. ⋯ Both dexmedetomidine and omega-conotoxin CVID completely inhibited allodynia (ED50 0.78+/-0.02 and 0.35+/-0.08 microg/kg, respectively; n=63, 41). Dexmedetomidine and omega-conotoxin CVID combined in dose ratios 0.7 and 1.3 (adjusted for ED50) were synergistic in decreasing mechanical hypersensitivity; interaction index (gamma) 0.39 (confidence interval [CI] 0.33, 0.46) and 0.3 (CI 0.23, 0.38). Despite the necessity for i.t. administration, these data suggest that the synergistic combination confers enhanced potency (lower doses) of both drugs that may avoid clinical toxicity of single drug therapy.
-
Randomized Controlled Trial Comparative Study Clinical Trial
Psychophysical outcomes from a randomized pilot study of manual, electro, and sham acupuncture treatment on experimentally induced thermal pain.
In this pilot study comparing the analgesic effects of three acupuncture modes--manual, electro, and placebo (with Streitberger placebo needles)--in a cohort of healthy subjects, we found that verum acupuncture treatment, but not placebo, lowered pain ratings in response to calibrated noxious thermal stimuli. This finding was mainly the result of highly significant analgesia in 5 of the 11 subjects who completed the 5-session study. Of the 5 responders, 2 responded only to electroacupuncture and 3 only to manual acupuncture, suggesting that acupuncture's analgesic effects on experimental pain may be dependent on both subject and mode. We developed a simple quantitative assessment tool, the Subjective Acupuncture Sensation Scale (SASS), comprised of 9 descriptors and an anxiety measure to study the relationship between the deqi sensation induced by acupuncture and the putative therapeutic effects of acupuncture. The SASS results confirm that the deqi sensation is complex, with all subjects rating multiple descriptors during each mode. We found significant correlations of analgesia with SASS ratings of numbness and soreness, but not with ratings of stabbing, throbbing, tingling, burning, heaviness, fullness, or aching. This suggests that attributes of the deqi sensation may be useful clinical indicators of effective treatment. ⋯ The results of this study indicate the existence of both individual subject and acupuncture mode variability in the analgesic effects of acupuncture. This suggests that switching acupuncture mode may be a treatment option for unresponsive patients.
-
Our aims were to determine whether subjects with painful bladder syndrome (PBS) demonstrate characteristics of visceral pain syndromes: visceral hyperalgesia, expanded loci of referral of bladder sensation, increased bladder pain with repetitive filling, lower thresholds to cutaneous stimulation in relevant dermatomes, abnormal response to repetitive cutaneous stimulation in relevant dermatomes, and also to develop easily applied measures for PBS pain evaluation and management. ⋯ PBS subjects demonstrate bladder hyperalgesia and may sense bladder discomfort at sites other than suprapubic. Rating of bladder discomfort and sensory mapping during cystometry usefully distinguishes between PBS subjects and controls.
-
Comparative Study
Activation of p38 MAPK in primary afferent neurons by noxious stimulation and its involvement in the development of thermal hyperalgesia.
Alterations in the intracellular signal transduction pathway in primary afferents may contribute to pain hypersensitivity. We demonstrated that very rapid phosphorylation of p38 mitogen-activated protein kinase occurred in dorsal root ganglion (DRG) neurons that were participating in the transmission of noxious signals. Capsaicin injection induced phosphorylated-p38 (p-p38) in small-to-medium diameter sensory neurons with a peak at 2 min after capsaicin injection. ⋯ Intrathecal administration of the p38 inhibitor, FR167653, reversed the thermal hyperalgesia produced by the capsaicin injection. Inhibition of p38 activation was confirmed by the decrease in the number of p-p38-IR neurons in the DRG following capsaicin injection. Taken together, these findings suggest that the activation of p38 pathways in primary afferents by noxious stimulation in vivo may be, at least in part, correlated with functional activity, and further, involved in the development of thermal hyperalgesia.
-
Indian J. Exp. Biol. · Jan 2005
Role of cyclooxygenase-2 in lipopolysaccharide-induced hyperalgesia in formalin test.
Lipopolysaccharide (LPS)-induced hyperalgesia and the role of cyclooxygenase (COX) isoforms in acute and chronic nociceptive assays have been well established. However, the role of COX isoforms in LPS-induced hyperalgesia in the formalin test is not clear. Thus, the present study was undertaken to characterize the time course of formalin-induced nociceptive response in LPS-pretreated mice and to investigate possible effects of COX inhibitors to address the potential role of COX isoforms in LPS-induced hyperalgesia in the formalin test. ⋯ In contrast, parecoxib (prodrug of valdecoxib, a selective COX-2 inhibitor) or dexamethasone (COX-2 transcription inhibitor), when administered intravenously or intraperitoneally, respectively, did not show antinociceptive effect in the formalin test in saline-pretreated mice. However, both the agents significantly and dose-dependently decreased the late phase nociceptive behaviour of the formalin test in LPS-pretreated mice to the level of the animals that received saline pretreatment. These results suggest that induction of COX-2 by proinflammatory mediators and subsequent release of prostaglandins could be responsible for LPS enhancement of formalin-induced nocifensive behaviour and supports an important role of COX-2 in LPS-induced hyperalgesia in the formalin test.