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Activation of the supraspinal pain inhibition system by ketamine hydrochloride
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Activation of the supr~pin~ pain inhibition system by ke~mine hydr~~o~de. - N. Tomemori, T. Komatsu, K. Shingu, N. Urabe, N. Seo and K. Mori (Dept. of Anesthesiology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan), Acta anaesth. stand., 25 (1981) 355-359. There is abundant clinical evidence for the potent analgesic action of ketamine. Nevertheless, an adequate explanation of the neural mechanisms involved has not been documented. Two different lines of investigations have been followed, one through depression of the thalamo-cortical system and the other through a direct action on the spinal cord dorsal horn. In this paper the neurophysiologic mechanism of ketamine-induced analgesia was studied in cats under conditions of electrolytic decerebration or pentobarbital anesthesia. Injection of bradykinin into the femoral artery served as the noxious stimulus and the neural response in the lateral funiculus of the spinal cord was recorded by the multi-unit activity technique. Ketamine depressed the bradykinininduced response more markedly in decerebrate, non-anesthetized cats than in pentobarbital-anesthetized cats. The depressant action disappeared following cervical cord transection at C,, in both decerebrate non-anesthetized and pentobarbitalanesthetized cats. Thus, the analgesic action of ketamine is probably exerted mainly through activation of the supraspinal pain inhibition system and a direct action on the spinal cord nociceptive neural mechanism, if any, is slight. The excitatory action of ketamine on the supraspinal pain inhibition system is susceptible to the depressant action of pentobarbital. Putative nocieeptive neuro~smi~e~ in the m~enceph~ic reticular fo~ation. H.J. Haigler and D.D. Spring (Dept. of Pharmacology, Emory University School of Medicine, Atlanta, Ga. 30322, U.S.A.), Life Sci., 29 (1981) 33-43. The mesencephalic reticular formation (MRF) of the rat is an area that is involved in nociception; morphine and met-enkephalin can act in this area to produce analgesia. However, the neurotransmitter(s) in the nociceptive pathway in the MRF have not been identified. Once these putative neurotransmitters are identified, it may be possible to determine the mechanism by which morphine and other analgesic agents produce analgesia in the MRF. Acetylcholine (ACh), substance P (SP), neurotensin (NT), norepinephrine (NE) and dopamine (DA) have all been implicated as putative neurotrans~tters involved in nociception. All of these compounds were ~croiontophoretica~y administered in the MRF of rats to determine which, if any, mimicked the effects produced by a nociceptive stimulus (foot pinch). This is only one of several criteria that a substance should meet to be considered a nociceptive neurotransmitter in the MRF. ACh and NE mimicked the effects of the nociceptive stimulus in 61% and 67% respectively of the cells tested: NT, DA and SP mimicked the effects of the nociceptive stimulus less frequently (33%, 30% 23% respectively). Therefore, the nociceptive neurotransmitters in the MRF appear to be ACh and NE; NT, DA and SP may be neurotransmitters with a less important role in nociception in the MRF.
Activation of the supr~pin~ pain inhibition system by ke~mine hydr~~o~de. - N. Tomemori, T. Komatsu, K. Shingu, N. Urabe, N. Seo and K. Mori (Dept. of Anesthesiology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan), Acta anaesth. stand., 25 (1981) 355-359. There is abundant clinical evidence for the potent analgesic action of ketamine. Nevertheless, an adequate explanation of the neural mechanisms involved has not been documented. Two different lines of investigations have been followed, one through depression of the thalamo-cortical system and the other through a direct action on the spinal cord dorsal horn. In this paper the neurophysiologic mechanism of ketamine-induced analgesia was studied in cats under conditions of electrolytic decerebration or pentobarbital anesthesia. Injection of bradykinin into the femoral artery served as the noxious stimulus and the neural response in the lateral funiculus of the spinal cord was recorded by the multi-unit activity technique. Ketamine depressed the bradykinininduced response more markedly in decerebrate, non-anesthetized cats than in pentobarbital-anesthetized cats. The depressant action disappeared following cervical cord transection at C,, in both decerebrate non-anesthetized and pentobarbitalanesthetized cats. Thus, the analgesic action of ketamine is probably exerted mainly through activation of the supraspinal pain inhibition system and a direct action on the spinal cord nociceptive neural mechanism, if any, is slight. The excitatory action of ketamine on the supraspinal pain inhibition system is susceptible to the depressant action of pentobarbital. Putative nocieeptive neuro~smi~e~ in the m~enceph~ic reticular fo~ation. H.J. Haigler and D.D. Spring (Dept. of Pharmacology, Emory University School of Medicine, Atlanta, Ga. 30322, U.S.A.), Life Sci., 29 (1981) 33-43. The mesencephalic reticular formation (MRF) of the rat is an area that is involved in nociception; morphine and met-enkephalin can act in this area to produce analgesia. However, the neurotransmitter(s) in the nociceptive pathway in the MRF have not been identified. Once these putative neurotransmitters are identified, it may be possible to determine the mechanism by which morphine and other analgesic agents produce analgesia in the MRF. Acetylcholine (ACh), substance P (SP), neurotensin (NT), norepinephrine (NE) and dopamine (DA) have all been implicated as putative neurotrans~tters involved in nociception. All of these compounds were ~croiontophoretica~y administered in the MRF of rats to determine which, if any, mimicked the effects produced by a nociceptive stimulus (foot pinch). This is only one of several criteria that a substance should meet to be considered a nociceptive neurotransmitter in the MRF. ACh and NE mimicked the effects of the nociceptive stimulus in 61% and 67% respectively of the cells tested: NT, DA and SP mimicked the effects of the nociceptive stimulus less frequently (33%, 30% 23% respectively). Therefore, the nociceptive neurotransmitters in the MRF appear to be ACh and NE; NT, DA and SP may be neurotransmitters with a less important role in nociception in the MRF.