No description available.

Controversy exists concerning the role that dopamine plays in analgesia. In the present studies, dopamine agonists produced analgesia, and D-amphetamine potentiated morphine analgesia, while treatment with 6-hydroxydopamine or mixed or selective D1 and D2 dopamine receptor antagonists attenuated or abolished morphine and D-amphetamine-induced analgesia, in the formalin test. Furthermore, microinjection of morphine into the ventral tegmental area (VTA) and ventral striatum produced analgesia, while intra-VTA microinjection of naloxone methylbromide antagonized the analgesia produced by systemic morphine, in the formalin test. In contrast, similar manipulations of dopamine had little or no effect in the tail flick test. Thus, dopamine appears to play a facilitatory role in formalin test analgesia, and there appear to be fundamental differences between the formalin and tail flick tests and parallels between the role of dopamine in the formalin test and in clinical pain, the vocalization after-discharge test and reward.

This series of experiments examined the neural mechanisms of analgesia caused by local anaesthetic blockade or selective blockade of N-methyl- scD-aspartate (NMDA) receptors at sites in the rat forebrain. Microinjections of the local anaesthetic lidocaine were made into the medial or lateral thalamic nuclei. The results indicate that the medial thalamic nuclei mediate the expression of pain behavior after peripheral injury, whereas the lateral thalamic nuclei influence phasic withdrawal responses, but are not critical for injury-induced pain responses. Electrolytic lesions made in the lateral thalamus verified this latter finding. Intracranial microinjections of the NMDA antagonist AP5 were used to determine if NMDA receptors in the forebrain participate in pain-related central processing. The intralaminar thalamic nuclei, the striatum and the dentate gyrus of the hippocampal formation were indicated as forebrain sites where antagonism of NMDA-sensitive neural mechanisms significantly reduced the expression of pain-related behavior in the formalin test.

The mechanisms of pain and hyperalgesia were examined in rats following cutaneous-heat and peripheral-nerve injury. Central mechanisms of hyperalgesia were indicated since a heat injury produced a decrease in foot-withdrawal latencies in the paw contralateral to the injury and an increase in autotomy of the injured paw following section of the sciatic and saphenous nerves. The reduced contralateral foot-withdrawal latencies were reversed by spinal anesthesia and subcutaneous guanethidine, but were unaffected by local anesthetics and capsaicin at the site of injury. The enhancement of autotomy produced by an injury was reduced by spinal anesthesia and a combination of intrathecal capsaicin and subcutaneous guanethidine. Both intrathecal substance P and systemic noradrenaline produced an increase in autotomy following nerve lesions; guanethidine, but neither capsaicin nor procaine, produced a decrease in autotomy. A reduction in inflammation and hyperalgesia within an injured paw was produced by local capsaicin, but not by guanethidine. The results suggest that central mechanisms, such as spinal hyperactivity, combined with peripheral neurogenic mechanisms are involved in the production of hyperalgesia following heat injury. Pain and hyperalgesia following nerve injury are proposed to be due to spinal cord plasticity resulting from deafferentation and abnormal sympathetic activity.

We investigated the role of two intracellular second messengers, extracellular signal-regulated protein kinase (ERK), and protein kinase C (PKC) in a model of persistent pain, using intrathecal (i.t) (R,S )-DHPG to induce spontaneous nociceptive behaviours (SNBs). SNBs were measured in animals that were treated with an ERK inhibitor (PD 98059), and a PKC inhibitor (GF 109203X) compared with controls. Mechanical allodynia, was measured using paw withdrawal thresholds in the von Frey test, and thermal hyperalgesia was measured using response latencies in the plantar test. In study 1, it was shown that spinal administration of PD 98059, dose-dependently decreased SNBs, and reduced mechanical allodynia and thermal hyperalgesia. In study 2, it was shown that i.t. pretreatment with the GF 109203X, reduced SNBs and thermal hyperalgesia, but not mechanical allodynia. These results suggest that both ERK and PKC are involved in SNBs and the concomitant and thermal hyperalgesia and possibly mechanical allodynia.

No description available.

No description available.

No description available.

This study examined central mechanisms of persistent pain using an autoradiographic technique to localize phosphoinositide hydrolysis (PI) in the rat spinal cord dorsal horn. The lateral half of laminae I-II showed the highest levels of baseline PI turnover and carbachol-stimulated PI turnover in normal animals as well as after inflammation. Inflammation resulted in increased baseline PI turnover in this region of the ipsilateral (76%) and contralateral (65%) dorsal horns. Carbachol increased PI turnover in this region in normal rats (55%) and following inflammation (ipsilateral: 46%, contralateral: 45%). The absolute magnitudes of these increases were 1.85, 2.71, and 2.51 nCi/mg, respectively. The results of this study demonstrate the involvement of PI turnover in neural mechanisms of persistent pain, and provide evidence for the involvement of cholinergic systems in this process. Because spinal cholinergic systems have been reported to be anti-nociceptive, the present results appear to reflect an upregulation of anti-nociceptive activity in response to inflammation. Thus, the spinal cholinergic system may be a regulatory site within the anti-nociceptive pathway, and may provide an attractive target for the development of new therapeutic agents.

Distinct brain regions process innocuous vibration and cutaneous heat pain. The role of these areas in the perception of pain is still a matter of debate; and the role of these areas in the mediation of memory of somatosensory stimuli is uncertain and has not been studied with brain imaging in healthy human volunteers. All experiments described here, involved an experimental design, which included a delayed-discrimination paradigm and functional magnetic resonance imaging (fMRI). In manuscript #1, we aimed at unraveling the cerebral correlates of attention and spatial localization of innocuous vibrotactile stimuli applied to the right volar surface of the forearm. In this study, we report that increased degrees of attention to the vibrotactile stimuli were associated with heightened levels of activation in several brain areas. In manuscript #2, we investigated the short-term memory for sensory aspects (intensity and location) of cutaneous heat pain delivered to two areas (thenar and hypothenar eminences) of the palm of the right hand. In this experiment, the memory and control trials were presented in blocks, whereby the subjects could predict what trials were going to follow. This study revealed that the presentation of painful stimuli evoked activation in different brain regions than those activated during the online maintenance (interstimulus interval or ISI) of the intensity and spatial features of those stimuli; a process, which I will refer to short-term memory. In manuscript #3, we investigated again short-term memory for sensory aspects of heat pain (as in manuscript #2), but in this case, the memory and control trials were presented in a randomized order. In this study, we found that the perception and short-term memory of pain were processed by a comparable network of areas. The predictability of the memory and control trials may have contributed to these findings. / La vibration inoffensive ainsi que la chaleur douloureuse cutanée sont traitées pardifférentes régions du cerveau. Le rôle de ces régions dans la perception de la douleurest controversé; et le rôle de ces régions dans la mémoire des stimuli somatosensorielsest incertain et n'a jamais encore été étudié en imagerie cérébrale chez des sujetshumains sains. Le design expérimental de toutes les études décrites ici comprenait unparadigme de 'delayed-discrimination' et l'imagerie par résonance magnétiquefonctionnelle (IRMf). L'étude #1 visait à élucider les corrélats cérébraux de l'attention etde la localisation spatiale des stimuli vibrotactiles inoffensifs présentés à la faceantérieure de l'avant-bras droit. Dans cette étude, nous avons trouvé que des degrésélevés d'attention portée aux stimuli vibrotactiles étaient associés à des niveaux accrusd'activation dans plusieurs zones du cerveau. Dans l'étude #2, nous avons enquêté surla mémoire à court-terme des caractéristiques sensorielles (intensité et emplacement)de la chaleur douloureuse cutanée présentée à deux endroits (éminences thénar ethypothénar) de la paume de la main droite. Dans cette étude, les essais mémoire etcontrôle étaient présentés en bloc, ou de sorte que les participants pouvaient prévoir dequel type serait le prochain essai. Cette étude a révélé que la présentation des stimulidouloureux a évoqué une activation de différentes régions cérébrales que celles quiétaient activées lors de la rétention de l'intensité et de l'emplacement des stimulationsdurant l'intervalle inter-stimuli (liS); un processus que je qualifierai de mémoire à courtterme.Dans l'étude #3, nous avons également enquêté sur la 'mémoire à court-termedes aspects sensoriels de la chaleur douloureuse (tout comme dans l'étude #2), maisdans ce cas, les essais mémoire et contrôle étaient présentés de façon aléatoire. Danscette étude, nous avons trouvé que la perception de la douleur ainsi que la mémoire àcourt-terme de la douleur étaient traitées par un réseau de régions semblable. Laprévisibilité des essais mémoire et contrôle peut avoir contribué à ce résultat.