Naloxone does not Antagonize the Anesthetic‐Induced Depression of Nociceptor‐Driven Spinal Cord Response in Spinal Cats

Abstract

The effects of several anaesthetics on spinal cord nociceptive neural mechanisms and their interactions with the opiate antagonist, naloxone, were studied in acute, spinal cord transected cats. Intra-arterial injection of bradykinin was used as the noxious test stimulus. Spontaneous activity and the neural response induced by bradykinin were recorded by the multi-unit activity technique in the lateral funiculus of the spinal cord. Naloxone, 0.1 or 2.0 mg/kg i.v. had little effect on the bradykinin-induced response, but enhanced the spontaneous firing of the lateral funiculus significantly. Fentanyl, 30 micrograms/kg i.v., depressed both the bradykinin-induced response and spontaneous firing. These effects of fentanyl were antagonized completely by naloxone, 0.1 mg/kg i.v. Nitrous oxide, thiamylal, halothane and ether depressed the bradykinin-induced response considerably, but it was not antagonized by naloxone, 0.1-2.0 mg/kg i.v. Enflurane had little effect on the bradykinin-induced response. The effects of these anesthetics on spontaneous firing were divergent: nitrous oxide enhanced it while other drugs depressed it, to various degrees. All these data suggest that the neural and/or neurochemical mechanisms of anesthetic-induced analgesia differ from mechanisms related to opioids.

Nociceptive spinal withdrawal reflexes but not spinal dorsal horn wide‐dynamic range neuron activities are specifically inhibited by halothane anaesthesia in spinalized rats

“…This suggests that low concentrations of halothane may not modulate the nociceptive responses of DH WDR neurons and SMUs EMG responses via spinal opioid µ‐receptors; in a previous investigation in our laboratory, naloxone similarly failed to affect the nociceptive responses of DH WDR neurons and of SMUs during 1% halothane‐induced anaesthesia in intact rat (You et al ., 2005). In addition, some studies have reported that general anaesthesia‐induced inhibition of nociceptive responses is insensitive to naloxone (Harper et al ., 1978; Shingu et al ., 1981). Accordingly, we could suppose that different concentrations of halothane may modulate the spinal signal transmission in the spinal DH area via different spinal multireceptors.…”

Projections from the mesopontine tegmental anesthesia area to regions involved in pain modulation

“…Recordings in spinally transected animals, and studies in which anesthetic agents are applied selectively to the spinal cord, suggest that direct drug actions on dorsal horn neurons contributes to anesthetic antinociception (Wall, 1967;Kitahata et al, 1975;Namiki et al, 1980;Shingu et al, 1981;Stein et al, 1987;Jewett et al, 1992;Collins et al, 1995;Uchida et al, 1995;Antognini and Carstens, 2002;Soja et al, 2002). A direct spinal action of anesthetics is also consistent with the observations that nociceptive responses of spinal neurons begin to be depressed at barbiturate doses too low to affect brainstem pain inhibitory pathways (Sandkuhler et al, 1987), and that the minimum alveolar concentration (MAC) of isoflurane sufficient to depress movement in response to noxious stimulation is not altered by decerebration or spinal block (Rampil et al, 1993;Rampil, 1994).…”