ABSTRACT
Recent research has shown that effective inhibition of pain by endogenous mechanisms is not exclusively generated within the central nervous system (CNS). Such intrinsic pain control can also occur in the periphery, mediated by an interaction between immune cells and peripheral sensory nerve endings. This neuroimmune link has emerged during studies concerning the peripheral antinociceptive actions of locally applied exogenous opioid receptor agonists. A prerequisite for the manifestation of such peripheral effects seems to be inflammation, accompanied by hyperalgesia of the tissue from which the nociceptive impulses arise. Opioid receptors are present on peripheral sensory nerves and are up-regulated during the development of inflammation. Their endogenous ligands, opioid peptides, are synthesized in circulating immune cells, which under pathological conditions, migrate preferentially to injured sites. Under environmental stressful stimuli or in response to releasing agents (e.g., corticotropin-releasing factor, cytokines) these immunocytes can secrete opioids to activate peripheral opioid receptors and to produce analgesia by inhibiting either the excitability of these nerves or the release of excitatory, proinflammatory neuropeptides. Suppression of the immune system abolishes these effects. This chapter will present the discoveries that led to this concept and therapeutic implications resulting therefrom.
