Habituation of the early pain-specific respiratory response in sustained pain

Neurokinin-l receptor and CL-opioid receptor agonists affect respiratory rh ythm when injected directly into the preBotzinger brainstem complex, which is the hypothesized site for respiratory rhythmogenesis in mammals (Science 286 (1999) 1566). Early stress-induced analgesia (SIA) is naloxone-insensi tive and as such considered independent of the activation of the mu -opioid system. Prolonged application of electrical shocks, however, produces anal gesia that is mediated by the Cc-opioid system (Science 208 (1980) 623). To gether these findings suggest that any early pain-specific increased respir ation should be attenuated in the tonic state of pain. Ten healthy, pain-fr ee female volunteer subjects participated in this experimental study involv ing deep acute and tonic pain. The experimental design included three condi tions: (1) baseline; (2) pain; and (3) a placebo control stimulus. Experime ntal pain was induced by the infusion of hypertonic saline into the massete r muscle. Infusion of isotonic saline in the contralateral masseter was use d as a control. Blinded subjects were randomly assigned to a particular seq uential order of the experimental stages, i.e. hypertonic saline infusion p receded the isotonic saline infusion or vice versa. Respiration rate, mean peak inspiratory and expiratory how rates, and the minute ventilation volum e quantified breathing. Results indicate that effects on respiration were p ain-specific and that the early effects on respiration were significantly a ttenuated in sustained pain. In the early stage of pain, all monitored vari ables (respiration rate, minute Ventilation volume, and inspiratory and exp iratory flow rates) were elevated to statistically significant degrees when compared to measurements taken at baseline or during control infusion. Onl y respiration rate continued to be significantly elevated in sustained pain . We concluded that rhythmogenic neurons in the preBotzinger brainstem comp lex appear as the likely target for pro-nociceptive and anti-nociceptive in put, explaining both the observed initial facilitation and subsequent habit uation of respiration in early and sustained pain. (C) 2001 International A ssociation for the Study of Pain. Published by Elsevier Science B.V. All ri ghts reserved.