Simultaneous depletion of neurokinin A, substance P and calcitonin gene-related peptide from the caudal trigeminal nucleus of the rat during electrical stimulation of the trigeminal ganglion

Abstract

The central terminals of the primary sensory trigeminal ganglion (TG) neurons projecting into the caudal trigeminal nucleus (CTN) of the rat exhibit neurokinin A (NKA)-, substance P (SP)-, and calcitonin gene-related peptide (CGRP)-immunoreactivities (IRs). We stimulated the TG in the rat to induce some of the alterations which might occur during migraine (neurogenic inflammation). Under a stereotaxic apparatus and by means of a bipolar electrode, one-side TG of the animals were electrically stimulated (7.5 Hz, 5 ms, 0.8-1. 4 mA) with square pulses for 5 min. Then, using immunohistochemical methods, the lower medulla of each rat was studied for NKA-, SP- and CGRP-IRs. Light microscopic examination of brain-stem sequencial sections revealed a simultaneous decrease in the immunoreactivities of all neuropeptides (NKA, SP and CGRP) in the CTN ipsilateral to TG stimulation in comparison with the other (not stimulated) side CTN. It is suggested that this decrease in immunoreactivity would be due to the co-release of neuropeptides following noxious stimuli and that NKA, SP and CGRP might therefore act as co-transmitters or co-modulators at the first central synapses of the trigeminal sensory pathway.

Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat

“…44 Subsequently, expression of SP transiently increased at 12 h. Intra-articular injection of a mixture of kaolin and carrageenan in rats led to decreased SP immunoreactivity in the dorsal horn, which subsequently increased by 8 h. 45 The authors suggested that the initial decrease was because of exocytosis of SP from presynaptic terminals in the superficial laminae, which was corroborated by other reports noting high SP concentration in the dorsal horn/cerebrospinal fluid, soon after noxious insults. 46,47 Further, the subsequent increase supposedly resulted from increased synthesis and axoplasmic transport of SP from cell bodies of DRG neurons and even brain stem neurons.…”

Role of neuropeptides in migraine: where do they stand in the latest expert recommendations in migraine treatment?

“…Consistent with this, Gallai et al [1995] found an increased CGRP and NKA levels in human blood during migraine attacks. Depletion of CGRP-immunoreactivity in the peripheral and central trigeminal terminals [Knyihár-Csillik et al, 1994, 1996], as well as the CGRP, SP, and NKA depletion in the CTN [Samsam et al, , 1999[Samsam et al, , 2000[Samsam et al, , 2001 has been reported following electrical stimulation of the rat TG.…”

“…Electrical stimulation of the TG results in the release of CGRP from the central terminals in the ipsilateral CTN [Knyihár-Csillik et al, 1998;Samsam et al, 1996Samsam et al, , 1999Samsam et al, , 2000. Such depletion is significant in CTN in the lower medulla, where the majority of the central terminals of the dull pain conveying unmyelinated C-fibers of the TG neurons terminate.…”

“…This is accompanied by an increase in the expression of the early gene, c-fos in the CTN, indicating the release of excitatory neurotransmitters from central trigeminal terminals located in the CTN [Knyihár-Csillik et al, 1997]. There is also a co-release of CGRP, SP and NKA from the trigeminal central neurons in the medulla oblongata [Samsam et al, 2000], indicating a possible co-transmitter or co-modulatory role of these neuropeptides in nociception.…”

Role of pituitary adenylate cyclase-activating polypeptide (pacap) in the trigeminovascular system: preclinical and clinical results

“…This is a well-described, widely used and generally certified method of TS activation with a broad range of stimulation parameters [99][100][101][102][103][104][105]. ES of the superior sagittal sinus can evoke a similar effect.…”