Articles: hyperalgesia.
-
Gabapentin, a gamma-aminobutyric acid analog anticonvulsant, has been shown to possess antinociceptive effects in animal models and clinical trials. An endogenous binding site of [3H]gabapentin has been revealed to be the alpha(2)delta subunit of voltage-dependent Ca2+ channels. Magnesium chloride, ruthenium red, and spermine have been shown to modulate [3H]gabapentin binding to this binding site in vitro. In this study, the authors examined whether intrathecal magnesium chloride, ruthenium red, or spermine could affect the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain. ⋯ These results provide behavioral evidence to support that the alpha(2)delta subunit of Ca2+ channels may be involved in the antiallodynic action of intrathecal gabapentin in the postoperative pain model.
-
Comparative Study
SYM 2081, an agonist that desensitizes kainate receptors, attenuates capsaicin and inflammatory hyperalgesia.
Excitatory amino acids acting at non-NMDA receptors contribute to transmission of nociceptive information. SYM 2081 ((2S,4R)-4-methyl glutamic acid) desensitizes kainate receptors, one subtype of non-NMDA receptors, to subsequent release of excitatory amino acids and thus may attenuate transmission of nociceptive information. To determine if SYM 2081 can prevent development of hyperalgesia, SYM 2081 (10, 50 or 100 mg/kg, i.p.) was administered prior to injection of capsaicin into the hindpaw of rats, which produces mechanical and heat hyperalgesia. ⋯ Intrathecal (1-100 microg/5 microl), but not intraplantar (10 or 100 microg/50 microl), injection of SYM 2081 attenuated the development of capsaicin-evoked heat hyperalgesia suggesting that SYM 2081's antihyperalgesic effects were due to its central effects. Furthermore, SYM 2081 completely reversed ongoing carrageenan-evoked mechanical hyperalgesia and partially (approximately 50%) reversed ongoing heat hyperalgesia. The present study demonstrates that administration of a high-potency ligand that selectively desensitizes kainate receptors attenuates the development of mechanical and heat hyperalgesia and attenuates ongoing inflammatory hyperalgesia.
-
Comparative Study
The alpha2A-adrenoceptor subtype is not involved in inflammatory hyperalgesia or morphine-induced antinociception.
The purpose of the present study was to investigate the role of the alpha(2A)-adrenoceptor subtype in inflammatory hyperalgesia, and in adrenergic-mu-opioid interactions in acute pain and inflammatory hyperalgesia. Behavioral responses to mechanical and thermal stimuli were studied in alpha(2A)-adrenoceptor knockout mice and their wild-type controls. Thermal nociception was evaluated as paw withdrawal latencies to radiant heat applied to the hindpaws. ⋯ Also, the antinociceptive effects of morphine in mechanical nociceptive tests were similar before and after carrageenan-induced hindpaw inflammation. Our observations indicate that alpha(2A)-adrenoceptors are not tonically involved in the modulation of inflammation-induced mechanical and thermal hyperalgesia. In addition, alpha(2A)-adrenoceptors do not appear to play an important role in mu-opioid receptor-mediated antinociception or antihyperalgesia.
-
Comparative Study Clinical Trial
Comparison of the pain suppressive effects of clinical and experimental painful conditioning stimuli.
Studies in healthy volunteers suggested that the classical counterirritation phenomenon (i.e. pain inhibits pain effect) might depend on diffuse noxious inhibitory controls (DNIC), which modulate the spinal transmission of nociceptive signals. In the present study, we sought to determine whether similar mechanisms were at play in patients with different subtypes of neuropathic pain. Ten patients presenting with a traumatic peripheral nerve injury associated with dynamic mechano-allodynia (i.e. pain triggered by brushing) or static mechano-allodynia (i.e. pain triggered by light pressure stimuli) were included in this study. ⋯ These effects were similar to those induced by HNCS and were probably due to an increased activation of DNIC. In contrast, in patients with dynamic allodynia, brushing within the allodynic area reduced the pain sensation at the foot, but did not inhibit the electrophysiological responses, suggesting that in this case the counterirritation effect may take place at the supraspinal level. Thus, the mechanisms of counterirritation are not univocal, but depend on the pathophysiological mechanisms of clinical pain.
-
Clinical Trial
Keeping pain out of mind: the role of the dorsolateral prefrontal cortex in pain modulation.
Frontal lobe activity during pain is generally linked to attentional processing. We addressed the question of whether 'bottom-up' processing and 'top-down' modulation of nociceptive information dissociate anatomically within the frontal lobe by using PET scanning during painful thermal stimulation of normal and capsaicin-treated skin. We showed recently that pain following normally non-painful heat stimuli on chemically irritated skin (heat allodynia) uniquely engages extensive areas of the bilateral dorsolateral prefrontal (DLPFC), ventral/orbitofrontal (VOFC) and perigenual anterior cingulate (ACC) cortices. ⋯ The inter-regional correlation of midbrain and medial thalamic activity was significantly reduced during high left DLPFC activity, suggesting that its negative correlation with pain affect may result from dampening of the effective connectivity of the midbrain-medial thalamic pathway. In contrast, right DLPFC activity was associated with a weakened relationship of the anterior insula with both pain intensity and affect. We propose that the DLPFC exerts active control on pain perception by modulating corticosubcortical and corticocortical pathways.