Comparison of antinociception induced by supraspinally administered l‐arginine and kyotorphin

Abstract

Intracerebroventricular (i.c.v.) or intracisternal (i.cist.) administration of kyotorphin (KTP), an endogenous Met‐enkephalin releaser, at 5 μg per mouse, and l‐arginine (l‐Arg), a possible KTP precursor, at 30 μg per mouse, elicited antinociception in mice to a similar extent, as assessed by the tail‐flick test. Intracisternal preadministration of anti‐KTP serum abolished the effects of i.cist. KTP and i.c.v. or i.cist. l‐Arg, but not of i.c.v. KTP. The antinociceptive effects of i.cist. KTP and of i.c.v. or i.cist. l‐Arg disappeared in reserpinized mice, whereas the effect of i.c.v. KTP was unaffected by treatment of mice with reserpine. Intrathecal (i.t.) phentolamine markedly reduced the antinocieption induced by i.cist. KTP and by i.c.v. or i.cist. l‐Arg, but not by i.c.v. KTP. Intrathecal methysergide attenuated the antinociceptive effects of i.cist. KTP, but not of i.c.v. KTP and i.c.v. or i.cist. l‐Arg. These results suggest that the antinociception produced by i.cist. KTP, but not by i.c.v. KTP, is mediated by the brainstem‐spinal noradrenergic and 5‐hydroxytryptaminergic systems, and that l‐Arg given i.c.v. or i.cist. increases KTP formation in the lower brain, possibly the brainstem, resulting in antinociception mediated by the descending noradrenergic system. Therefore, the regional distribution of KTP receptors and KTP synthetase in the brain does not appear to be common.

Studies on kyotorphin and d-kyotorphin in aqueous solution by Raman spectroscopy

“…The analgesia induced by kyotorphin lasts longer than that induced by Met-enkephalin. The analogue D-kyotorphin [L-Tyrosine-D-Arginine] (D-KTP) produces also analgesic effects by the introduction of Met-enkephalin release [1][2][3]. D-KTP is found to be more stable enzymatically in the brain therefore shows higher in vivo analgesic activity than does KTP [2,3].…”

“…It displays opioid type actions, including analgesic effects by releasing opioid pentapeptide Met-enkephalin from slices of the brain and spinal cord [1]. The analgesia induced by kyotorphin lasts longer than that induced by Met-enkephalin.…”

Effects of multiple intrathecal administration of L-arginine with different doses on formalin-induced nociceptive behavioral responses in rats

“…It has been demonstrated that NO may have pronociceptive effects [1,2,11,12] or exert antinociception [3,13] at the spinal cord level. Others report that NO produces dual effects on nociception, depending on the dose and the pain model [6] .…”

“…Reports have shown that intracerebroventricular (i.c.v.) injection of L-arginine (L-Arg) can elicit antinociception in mice [3] . Another study suggests that NO plays dual roles in nociception in the brain or in the periphery [4,5] .…”

NADPH-d and Fos reactivity in the rat spinal cord following experimental spinal cord injury and embryonic neural stem cell transplantation

“…NO is also part of the NMDA (N-Methyl-D-aspartic acid) receptor-coupled mechanism responsible for the activation of the c-fos gene (Garthwaite et al, 1988) and diffuses from neuronal cell bodies or dendritic/axonal processes to induce Fos expression in neighboring neurons (Salter et al, 1996). NOS inhibitors reduce Fos expression as well as nociceptive behavior following formalin injection in the hind paw (Chapman et al, 1995;Kawabata et al, 1994;Roche et al, 1996).…”