Pain
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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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Activation of adenosine A1 receptors by endogenous adenosine or synthetic agonists produces anti-nociception in animal models of acute pain and also reduces hypersensitivity in models of inflammatory and nerve-injury pain. Allosteric adenosine modulators facilitate adenosine agonist binding to the A1 receptor. The purpose of the current study was to examine the effect, mechanisms of action, and interaction with noradrenergic systems of intrathecal (i.t.) or oral administration of the allosteric adenosine modulator T62 in a rat model of neuropathic pain. ⋯ Anti-dopamine hydroxylase (DH)-saporin treatment reduce spinal norepinephrine content by 97%, accompanied by an almost complete loss of DH immunoreactive axons in the spinal dorsal horn and neurons in the locus coeruleus. The effect of T62 was completely lost in animals treated with anti-DH-saporin. These data support the hypothesis that activation of the A1 receptor by the allosteric modulator, T62, produces anti-nociception via spinal noradrenergic activation.
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Recent research has focused on prostaglandins in the central nervous system and their contribution to hyperalgesia and allodynia. This study sought to establish whether neurokinin-1 (NK-1) receptors and glutamate receptors are involved in the hyperalgesic and allodynic effects of spinally administered prostaglandin E2 (PGE2) in rats, and also to determine if the same receptors are involved the hyperalgesia induced by intraplantar administration of zymosan, an inflammatory agent which is known to evoke spinal PGE2 release. Spinal application of antagonists of the NK-1 receptor, the -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate glutamate or metabotropic glutamate receptor significantly attenuated the decrease in mechanical paw withdrawal response thresholds produced by either spinal administration of PGE2 or intraplantar administration of zymosan. ⋯ These results suggest that both PGE2-induced and zymosan-induced mechanical hyperalgesia are mediated in part through activation of NK-1, AMPA/kainate and metabotropic glutamate receptors. PGE2-induced, but not zymosan-induced, thermal hyperalgesia is mediated in part by activation of NMDA, AMPA/kainate and metabotropic glutamate receptors. Activation of both NMDA and AMPA/kainate receptors contribute to PGE2-induced allodynia.
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The effects of intrathecal (i.t.) administration of prostaglandin E2 (PGE2) and prostaglandin F2 (PGF2) on behavioral and spinal neuronal responses to mechanical and thermal stimuli were examined in rats. i.t. Administration of either PGE2 (1-100 nmol) or PGF2 (1-100 nmol) produced a robust, dose-dependent mechanical hyperalgesia, but only a weak thermal hyperalgesia and touch-evoked allodynia. Spinal administration of either PGE2 (100 pmol-100 nmol) or PGF2 (1-100 nmol) produced dose-dependent increases in responses of nociceptive specific (NS) neurons to mechanical stimuli, but only modest increases in wide dynamic range (WDR) neurons to mechanical stimuli. ⋯ Both PGE2 and PGF2 produced increases in background discharges of WDR and NS neurons, although this effect was most consistently observed with WDR neurons and PGE2. These behavioral and electrophysiological data suggest that mechanical hyperalgesia induced by spinal administration of PGE2 and PGF2 is mediated mainly by changes in NS neurons. The weak thermal hyperalgesia may reflect changes in WDR neurons.