Neuroscience
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Detailed electrophysiological characterisation of spinal opioid receptors in the mouse has been limited due to various technical difficulties. In this study, extracellular single unit recordings were made from dorsal horn neurones in a perfused spinal cord with attached trunk-hindquarter to investigate the role of delta-opioid receptor in mediating nociceptive and non-nociceptive transmission in mouse. Noxious electrical shock, pinch and heat stimuli evoked a mean response of 20.8+/-2.5 (n=10, P<0.005), 30.1+/-5.4 (n=58, P<0.005) and 40.9+/-6.3 (n=29, P<0.005) spikes per stimulus respectively. ⋯ In contrast, the responses of non-nociceptive dorsal horn neurones were not inhibited by SNC 80 at a dose of up to 10 microM (n=5). These data demonstrate that delta-opioid receptor modulate nociceptive, but not non-nociceptive, transmission in spinal dorsal horn neurones of the adult mouse. The potentiation of neuronal activity by HS 378 may reflect an autoregulatory role of the endogenous delta-opioid in nociceptive transmission in mouse.
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Selection line rats congenitally high or low for autotomy in the neuroma model of neuropathic pain (HA and LA rats) were found to be correspondingly high and low in a second type of neuropathic pain, the Chung model, which employs an alternative phenotypic endpoint, tactile allodynia. It has been proposed that both phenotypes reflect ectopic hyperexcitability in axotomized primary sensory neurons. ⋯ However, in the one neuronal subclass previously linked to neuropathic pain in these models the increase was significantly greater in HA than LA rats, and only at the time when pain scores in the two lines were diverging. Heritable differences in electrical response to axotomy in a specific afferent cell type appear to be a fundamental determinant of neuropathic pain.
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Nerve injury often leads to chronic, sometimes excruciating, pain. The mechanisms contributing to this syndrome include neurochemical plasticity in neurons involved in the earliest stages of pain transmission. Endomorphin-2 (Tyr-Pro-Phe-Phe-NH(2)) is an endogenous morphine-like substance that binds to the mu-opioid receptor with high affinity and selectivity. ⋯ Both thermal hyperalgesia, as evidenced by significantly decreased paw withdrawal latencies, and decreased endomorphin-2-LI were observed within 2 days of injury and were most pronounced at 2 weeks after injury. The decrease in endomorphin-2-LI during the development of chronic pain is consistent with the loss of an inhibitory influence on pain transmission. These results provide the first evidence that reduction of an endogenous opioid in primary afferents is associated with injury-induced chronic pain.
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In humans with absence epilepsy, spike-and-wave discharges develop in the thalamocortical system during quiet immobile wakefulness or drowsiness. The present study examined the initial stage of the spontaneous development of spike-and-wave discharges in Genetic Absence Epilepsy Rats from Strasbourg. Bilateral electrocorticograms were recorded in epileptic and non-epileptic rats under freely moving and undrugged conditions and under neuroleptanalgesia. ⋯ Such oscillations are not themselves sufficient to initiate spike-and-wave discharges, meaning that genetic factors render thalamocortical networks prone to generate epileptic electrical activity, possibly by decreasing the excitability threshold in reticular cells. While these GABAergic neurons play a key role in the synchronization of glutamatergic relay neurons during seizures, relay cells may participate significantly in the regulation of the recurrence of the spike-and-wave complex. Furthermore, it is very likely that synchronization of relay and reticular cellular discharges during absence seizures is generated in part by corticothalamic inputs.
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We determined whether chronic neuropathy changes response properties of neurons in the rostroventromedial medulla of rats, and whether (d-Tyr)L(Me-Phe)QPQRF-amide, a neuropeptide FF analogue, in the periaqueductal gray produces changes in responses of rostroventromedial medullary neurons that might underlie its antiallodynic effect described earlier. Single unit recordings of medullary neurons were performed in lightly anesthetized neuropathic and control animals. Spontaneous activity and the responses to noxious thermal and mechanical stimulation of the hind paw were determined with and without administration of (d-Tyr)L(Me-Phe)QPQRF-amide. ⋯ Also, light pentobarbitone anesthesia markedly attenuated, but did not abolish, behaviorally determined neuropathic symptoms. From these results we suggest that NEUTRAL-neurons of the rostroventromedial medulla may have a role in neuropathy and they may be involved in attenuation of mechanical hypersensitivity by (d-Tyr)L(Me-Phe)QPQRF-amide in the periaqueductal gray. It is proposed that in neuropathy the synaptic effects of descending impulses from medullary NEUTRAL-neurons on their axonal targets in the spinal cord are changed so that this contributes to mechanical hypersensitivity, due to mechanisms that are at least partly serotoninergic.