The neurobiology of pain
- 1 May 1999
- journal article
- review article
- Published by Elsevier BV in The Lancet
- Vol. 353 (9164), 1610-1615
- https://doi.org/10.1016/s0140-6736(99)01313-6
Abstract
Understanding the plasticity of pain and analgesia exhibited in different pain states may improve therapies for the two major types of pain, neuropathic and inflammatory pain, in which nerve and tissue damage leads to alterations at both peripheral and central levels. At the level of the peripheral nerve, drugs that act on particular sodium channels may target only pain-related activity. Agents that act on some of the peripheral mediators of pain may control peripheral nerve activity. A new generation of non-steroidal anti-inflammatory drugs, cyclo-oxygenase 2 inhibitors, that lack gastric actions are becoming available. In the spinal cord, the release of peptides and glutamate causes activation of multiple receptors, particularly, the N-methyl-D-aspartate receptor for glutamate, which, in concert with other spinal systems, generates spinal hypersensitivity. Blocking the generation of excitability is one approach, but increasing inhibitions may also provide analgesia. Opioid actions are via presynaptic and post-synaptic inhibitory effects on central and peripheral C fibre terminals, spinal neurones, and supraspinal mechanisms. Our knowledge of brain mechanisms of pain is still, however, limited. Other new targets have been revealed by molecular biology and animal models of clinical pain, but the possibility of a "magic bullet" is doubtful. Thus, another approach could be single molecules with dual drug actions, that encompass targets where additive or synergistic effects of different mechanisms may enable pain relief without major adverse effects.Keywords
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