Pain
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Previous studies indicate that descending modulation of nociception is progressively increased following persistent inflammation. The present study was designed to further examine the role of supraspinal neurons in descending modulation following persistent inflammation. Constant levels of paw withdrawal (PW) and tail flick (TF) latencies to noxious heat stimuli were achieved in lightly anesthetized rats (pentobarbital sodium 3-10 mg/kg/h, i.v.). ⋯ Compared to vehicle-injected animals, microinjection of a soma-selective excitotoxin, ibotenic acid, enhanced ES-produced inhibition at 3 h but not at 24 h after inflammation. We propose that these time course changes reflect dynamic alterations in concomitant descending facilitation and inhibition. At early time points, NMDA receptor and NGC activation enhance descending facilitation; as time progresses, the dose-response curve of NMDA shifts to the left and descending inhibition dominates and masks any descending facilitation.
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Cannabinoids have previously been shown to possess analgesic properties in a model of visceral hyperalgesia in which the neurotrophin, nerve growth factor (NGF), plays a pivotal role. The purpose of this study was to investigate the antihyperalgesic effects of two cannabinoids in NGF-evoked visceral hyperalgesia in order to test the hypothesis that endocannabinoids may modulate the NGF-driven elements of inflammatory hyperalgesia. Intra-vesical installation of NGF replicates many features of visceral hyperalgesia, including a bladder hyper-reflexia and increased expression of the immediate early gene c fos in the spinal cord. ⋯ However, neither CB1 nor CB2 receptor antagonists altered the action of anandamide. PEA-induced reduction in Fos expression was abrogated by SR144528. These data add to the growing evidence of a therapeutic potential for cannabinoids, and support the hypothesis that the endogenous cannabinoid system modulates the NGF-mediated components of inflammatory processes.
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Comparative Study
Gender differences in temporal summation of mechanically evoked pain.
Several studies indicate that females are more sensitive to experimentally induced pain than males. Moreover, it was recently shown that temporal summation of heat pain is greater in females than males, suggesting that central processing of nociceptive input may be upregulated in women. Temporal summation of pain has been examined principally using thermal or electrical stimuli. ⋯ Temporal summation occurred across all ISIs, but shorter ISIs (1-3 s) elicited significantly greater temporal summation than longer ISIs (4-6 s). Finally, although higher pain ratings were obtained when the ten consecutive stimuli were applied on the same versus different skin areas, the degree of temporal summation was not significantly different. These findings indicate that temporal summation of mechanically evoked pain is higher in females compared to males, is stimulation frequency dependent and is centrally mediated.
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Rectal stimulation under normal or pathological conditions evokes numerous sensations. Previous studies have examined rectal stimulation-evoked pain and urge to defecate, but discrepancies in the findings remain because of the different methodologies used in each study and the reporting of sensations only at the end of or after the applied stimuli. Therefore, we conducted a psychophysical study of various aspects of rectal sensation in normal subjects using a variety of distension stimuli and continuous on-line rating of sensation. ⋯ Therefore, we conclude (1) Differences in the discrimination and the temporal characteristics of urge at subpainful rectal pressures and of pain at noxious pressures suggest that noxious and non-noxious stimuli are processed differently. (2) The overall unpleasantness and pain correlate with rectal volume during accommodation. However, instantaneous evoked sensations can vary independent of volume changes during constant pressure distension. (3) The reported sensation-related responses to tension and stretch will likely be different depending on the degree of accommodation that is occurring. Moreover, the peripheral receptor mechanisms which contribute to controlling this accommodation will also affect the perception of rectal stimuli. (4) Continuous ratings of rectal sensations are valuable in investigating rectal physiology and the multidimensional nature of rectal symptoms.
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Hypersensitivity after tissue injury is an expression of neuronal plasticity in the central nervous system. This has been explored most extensively using in vitro preparations and animal models of inflammatory pain and chemical irritation. For pain after surgery, a similar process has been proposed. ⋯ Sensitization was re-established in seven of eight neurons 2 h after injection as the local anesthetic dissipated. These results indicate that activation of DHNs during plantar incision and sensitization 1 h later are not necessary for subsequent pain behaviors. Because sensitization was reversed 90 min after plantar incision and then re-established as the local anesthetic effect diminished, enhanced responsiveness of DHN requires ongoing afferent input during the first day after incision.