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Spinal antinociception: clinical aspects.

Abstract

Recent research has demonstrated the increasing importance of the spinal cord in processing and modulating nociceptive input. Different groups of drugs, each acting by a unique mechanism, have been shown to block nociceptive afferent transmission. None of the currently available spinally administered local anesthetics, opioids or non-opioids produce analgesia without side effects. Non-opioids such as alpha-2-adrenergic agonists may be more suited as adjuvants rather than sole analgesic agents and their main role lies in reducing the dose requirements of other analgesics. Spinal somatostatin and ketamine may have neurotoxic potential. The role of these drugs and of midazolam in pain management appears to be limited. Preliminary results suggest that the neuropeptide octreotide has potent analgesic effects. 'Balanced spinal analgesia' using a combination of low doses of drugs, with separate but synergistic mechanisms of analgesia, may produce the best results. The optimal drug combinations and dosages remain to be determined. It is essential that animal neurotoxicity studies followed by controlled clinical trials are performed before widespread spinal administration of new drugs.

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BibTeXRIS

N Rawal. 1995. Spinal antinociception: clinical aspects.. https://doi.org/10.3109/07853899509031969

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Adrenergic alpha-Agonists↗

Presynaptic alpha-adrenoceptors in median preoptic nucleus modulate inhibitory neurotransmission from subfornical organ and organum vasculosum lamina terminalis.

The median preoptic nucleus (MnPO) in the lamina terminalis receives a prominent catecholaminergic innervation from the dorsomedial and ventrolateral medulla. The present investigation used whole cell patch-clamp recordings in rat brain slice preparations to evaluate the hypothesis that presynaptic adrenoceptors could modulate GABAergic inputs to MnPO neurons. Bath applications of norepinephrine (NE; 20-50 microM) induced a prolonged and reversible suppression of inhibitory postsynaptic currents (IPSCs) and reduced paired-pulse depression evoked by stimulation in the subfornical organ and organum vasculosum lamina terminalis. These events were not correlated with any observed changes in membrane conductance arising from NE activity at postsynaptic alpha(1)- or alpha(2)-adrenoceptors. Consistent with a role for presynaptic alpha(2)-adrenoceptors, responses were selectively mimicked by an alpha(2)-adrenoceptor agonist (UK-14304) and blockable with an alpha(2)-adrenoceptor antagonist (idazoxan). Although the alpha(1)-adrenoceptor agonist cirazoline and the alpha(1)-adrenoceptor antagonist prazosin were without effect on these evoked IPSCs, NE was noted to increase (via alpha(1)-adrenoceptors) or decrease (via alpha(2)-adrenoceptors) the frequency of spontaneous and tetrodotoxin-resistant miniature IPSCs. Collectively, these observations imply that both presynaptic and postsynaptic alpha(1)- and alpha(2)-adrenoceptors in MnPO are capable of selective modulation of rapid GABA(A) receptor-mediated inhibitory synaptic transmission along the lamina terminalis and therefore likely to exert a prominent influence in regulating cell excitability within the MnPO.

Adrenergic alpha-Agonists↗