Acute muscle inflammation enhances the monosynaptic reflexes and c-fos expression in the feline spinal cord

Chemical irritation of the lower urinary tract (LUT) of the rat increases the expression of the immediate early gene c-fos within neurons in the dorsal horn (DH), dorsal commissure (DCM), and intermediolateral region, including sacral parasympathetic nucleus (SPN) of the spinal cord (L6-S1). A previous study indicated the involvement of the N-methyl-D-aspartic acid (NMDA) receptor in this c-fos expression after LUT irritation. The role of glutamatergic synapses was further investigated using a selective and competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist (LY-215490). Systemic administration of LY-215490 produced a dose-dependent decrease in the number of Fos-positive cells after LUT irritation in the DCM and SPN areas, whereas in the DH only the highest dose (10 mg/kg) of LY-215490 decreased the number of Fos-positive cells. A low dose (1 mg/kg) of either MK-801 (an NMDA antagonist) or LY-215490 alone did not alter c-fos expression. However, a combined administration of low doses of MK-801 and LY-215490 significantly decreased the number of Fos-positive cells in all regions of the spinal cord. These results indicate that AMPA as well as NMDA receptors are involved in the spinal processing of nociceptive input from the LUT and that these glutamatergic receptors play a synergistic role in visceral nociceptive processing.

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Concomitant Administration of Morphine and an N-Methyl-D-Aspartate Receptor Antagonist Profoundly Reduces Inflammatory Evoked Spinal c-Fos Expression

Anesthesiology ◽

10.1097/00000542-199607000-00021 ◽

1996 ◽

Vol 85 (1) ◽

pp. 150-160 ◽

Cited By ~ 36

Author(s):

Prisca D. Honore ◽

Victoria Chapman ◽

Jaroslava Buritova ◽

Jean-Marie Besson

Keyword(s):

Spinal Cord ◽

Concomitant Administration ◽

Receptor Activation ◽

Intraplantar Injection ◽

Receptor Antagonism ◽

Mu Opioid ◽

Nociceptive Transmission ◽

Aspartate Receptor ◽

Fos Expression ◽

Two Parameters

Background After intraplantar injection of carrageenin, peripheral inflammation and spinal c-Fos expression are extensive, with the latter being sensitive to both large doses of morphine or N-methyl-D-aspartate receptor antagonism. The authors investigated the effects of coadministered morphine and (+)-HA966, a functional antagonist at the glycine site of the N-methyl-D-aspartate receptor, on the two parameters. Methods The effects of morphine, (+)-HA966 and coadministration of morphine and (+)-HA966 on spinal c-Fos expression in segments L4-L5 of the spinal cord and peripheral edema, induced at 1.5 h and 3 h after intraplantar carrageenin (6 mg/150 microliters) were studied. Results Previous coadministration of 0.3 mg/kg systemic morphine and 2.5 mg/kg subcutaneous (+)-HA966 significantly reduced c-Fos expression induced 1.5 h, but not 3 h, after carrageenin administration. However, coadministration of a larger dose of morphine (3 mg/kg) with (+)-HA966 (2.5 mg/kg) reduced c-Fos expression at 3 h after carrageenin administration, in a partially naloxone-reversible manner. Conclusions Concurrent mu-opioid receptor activation and N-methyl-D-aspartate receptor antagonism reduces nociceptive transmission at the level of the spinal cord, as shown by the reduction of carrageenin-evoked c-Fos expression.

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Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation

AJP Renal Physiology ◽

10.1152/ajprenal.00274.2004 ◽

2005 ◽

Vol 288 (3) ◽

pp. F466-F473 ◽

Cited By ~ 35

Author(s):

Satoshi Seki ◽

Kristin A. Erickson ◽

Masako Seki ◽

Osamu Nishizawa ◽

Yasuhiko Igawa ◽

...

Keyword(s):

Spinal Cord ◽

Dorsal Horn ◽

Intrathecal Administration ◽

Superficial Layer ◽

Sprague Dawley ◽

Intrathecal Catheter ◽

Micturition Reflex ◽

Nociceptive Responses ◽

Fos Expression ◽

Neurokinin 1

Substance P (SP) binding to neurokinin 1 receptors (NK1R) in the spinal cord reportedly plays an important role in the micturition reflex as well as in nociceptive responses. We therefore investigated the effect of ablation of NK1R-expressing neurons in the spinal cord using saporin, a ribosome-inactivating protein, conjugated with [Sar9, Met (O2)11]SP, a specific ligand of NK1R (SSP-saporin), on the micturition reflex in rats. In female Sprague-Dawley rats, SSP-saporin (1.0 or 1.5 μM) or saporin (1.5 μM) only was injected through an intrathecal catheter implanted at the L6-S1 level of the spinal cord. Three weeks after intrathecal administration of SSP-saporin, NK1R immunoreactivity in lamina I of the spinal cord was significantly reduced, but cystometric parameters in awake rats were not altered. Instillation of capsaicin (15 μM) into the bladder of normal rats induced bladder overactivity. This response to capsaicin was significantly suppressed in SSP-saporin-treated animals. SSP-saporin treatment also decreased c- fos expression in the dorsal horn of the spinal cord induced by instillation of capsaicin into the bladder. These data indicate that NK1R-expressing neurons in the superficial layer of the dorsal horn play an important role in transmission of nociceptive afferent information from the bladder to induce bladder overactivity and spinal c- fos expression elicited by bladder irritation. Toxin-induced damage of NK1R-expressing neurons in the lumbosacral spinal cord may provide an effective modality for treating overactivity and/or nociceptive responses in the bladder without affecting normal micturition.

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