The hypotension evoked by visceral nociception is mediated by delta opioid receptors in the periaqueductal gray

This study tested the hypothesis that the ventrolateral column of the midbrain periaqueductal gray (vlPAG) region mediates the hypotension and bradycardia evoked by visceral nociception. To test this, the local anesthetic lidocaine (2%; 0.5 microl) was microinjected into the vlPAG of halothane-anesthetized rats bilaterally and visceral nociception was induced 2 min later by injecting 5% acetic acid (0.5 ml) intraperitoneally. Acetic acid injection caused an abrupt fall in arterial pressure (-12.2+/-2.1 mm Hg) and heart rate (-37+/-93 bpm) lasting approximately 15 min. Lidocaine injection into the vlPAG prevented the fall in arterial pressure and heart rate completely. Cobalt chloride (5 mM; 0.2 or 0.5 microl) injection into the vlPAG also prevented nociceptive hypotension but it did not affect the fall in heart rate significantly. Lidocaine pretreatment also inhibited the depressor response caused by intramuscular formalin (5%; 0.2 ml) administration, a model of deep somatic nociception, although it did not prevent the response completely. To determine if opioid receptors mediate the response, selective mu, delta or kappa opioid receptor antagonists were microinjected into the vlPAG 5 min before intraperitoneal (ip) acetic acid administration. Naltrindole, a delta receptor antagonist, inhibited the response significantly but mu and kappa antagonists were completely ineffective. Lidocaine and naltrindole had no effect when injected into the dorsolateral PAG and did not influence cardiovascular function when injected into the vlPAG of saline treated control animals. These data support the hypothesis that the vlPAG mediates the depressor response evoked by visceral nociception and indicate that delta opioid receptors participate in the response.