The Effect of D-phenylalanine on the Analgesia Produced by Peripheral Nerve Conditioning Stimulation in the Cat

ABSTRACT

An effect of D-phenylalanine on the pain inhibitory mechanism of prolonged electrical stimulation of the peripheral nerve was studied in decerebrate cats and spinal cats. The response of spinal neurons was elicited either by electrical stimulation of the ipsilateral common peroneal nerve and tibial nerve. The single-unit activity of motor neurons which represent the flexion reflex was recorded from a filament of ventral rootlet divided from either the L7, S1 or S2 ventral root, and activity of dorsal horns cells was recorded with a microelectrode at the lumbosacral cord The conditioning stimuli which provocate the pain inhibitory mechanism of the common peroneal or tibial nerve was applied with repetitive, low frequency (2Hz), at a suprathreshold intensity for C fiber, for 30-45 minutes. The results of the experiment are summarized as follows 1. Applying conditioning stimuli produced a powerful inhibition of the responses which was provocated by noxious stimuli in either the decerebrate or the spinal cat without any statistical difference, and this effect can be observed for 15 minutes after the cessation of the conditioning stlmuli 2. This response was reversed completely by systemic injection of a specific opiate antagonist, naloxone. It suggests that the conditioning stimulus of the peripheral nerve can produce the endogenous opiate related pain inhibitory effect as the spinal mechanism. 3. The conditioning stimuli can produce the analgesic effect by means of supression of the activity of the dorsal horn cell which was related to the pain response in the decerebrate cat. The same result could be observed in flexion reflex. 4. D-phenylalanine, a putative inhibitor of carboxypeptidase which degradates the endogenous opiate-enkephalin, was studied in this experiment under the hypothesis that D-phenylalanine will emphasize or prolongate the action of enkephalin. But, intravenously injected D-phenylalanine did not potentiate the inhibitory effect of the conditioning stimuli of the peripheral nerve. From the above result, it is speculated that the electrical stimulation of the peripheral nerve is directly mediated by an endogenous opiate related analgesia, and the site of the analgesic action resides mainly in spinal cord level. But these data could not support the gypothesis that antinociceptive effect of D-phenylalanine results frm the potentiation of endogenously released enkephalin.