Tissue Injury Regulates Serotonin 1D Receptor Expression: Implications for the Control of Migraine and Inflammatory Pain

Abstract

The anti-migraine action of "triptan" drugs involves the activation of serotonin subtype 1D (5-HT 1D ) receptors expressed on "painresponsive" trigeminal primary afferents. In the central terminals of these nociceptors, the receptor is concentrated on peptidergic dense core vesicles (DCVs) and is notably absent from the plasma membrane. Based on this arrangement, we hypothesized that in the resting state the receptor is not available for binding by a triptan, but that noxious stimulation of these afferents could trigger vesicular release of DCVs, thus externalizing the receptor. Here we report that within 5 min of an acute mechanical stimulus to the hindpaw of the rat, there is a significant increase of 5-HT 1D -immunoreactivity (IR) in the ipsilateral dorsal horn of the spinal cord. We suggest that these rapid immunohistochemical changes reflect redistribution of sequestered receptor to the plasma membrane, where it is more readily detected. We also observed divergent changes in 5-HT 1D -IR in inflammatory and nerve-injury models of persistent pain, occurring at least in part through the regulation of 5-HT 1D -receptor gene expression. Finally, we found that 5-HT 1D -IR is unchanged in the spinal cord dorsal horn of mice with a deletion of the gene encoding the neuropeptide substance P. This result differs from that reported for the Ѩ-opioid receptor, which is also sorted to DCVs, but is greatly reduced in preprotachykinin mutant mice. We suggest that a "pain"-triggered regulation of 5-HT 1D -receptor expression underlies the effectiveness of triptans for the treatment of migraine. Moreover, the widespread expression of 5-HT 1D receptor in somatic nociceptive afferents suggests that triptans could, in certain circumstances, treat pain in nontrigeminal regions of the body.

Regulation of κ-Opioid Receptor Signaling in Peripheral Sensory Neurons In Vitro and In Vivo

“…were 1.09 Ϯ 0.21 (n ϭ 3) for vehicle conditions, 2.28 Ϯ 0.29 (n ϭ 7) for BK-pretreated cells, and 1. (Ahn and Basbaum, 2006) and receptors for neuropeptide Y (NPY) (Gibbs et al, 2007). Figure 4 shows that inhibition of PGE 2 -stimulated adenylyl cyclase activity occurred without BK pretreatment in response to maximal concentrations of the 5-HT 1 agonist 5-carboxamidotryptamine (5-CT) or by the NPY 1 receptor agonist Leu-Pro NPY (L,P-NPY).…”

Reversal of Inflammatory and Noninflammatory Visceral Pain by Central or Peripheral Actions of Sumatriptan

“…33 However, both the 5HT1 B and the 5HT1 D receptor are found in trigeminal and dorsal root ganglia 345, 6, 35, 36 suggesting that triptan actions at these receptors may also be a site of action for headache pain. As the distribution of 5HT1 B/D receptors is not unique to the trigeminal system, the apparent specific actions of triptans in headache pain 20 is puzzling.…”

Scorpion Toxins Modify Phytopathogenic Fungus Physiology. A Possible Source of New Fungicides

“…Fluorescence was measured from the pictures as integrated optical density (IOD) inside the mycelium and in its neighboring medium using the ImageJ 1.41 computer program (http://rsbweb.nih.gov/ij/). 25 The IOD was measured (before and 0.5, 1, 5, and 10 min after the addition of venom or isolated toxins) in 14 randomly selected areas, 7 in the central cytoplasmic hyphae region and 7 at the immediate vicinity of the same hyphae. The IOD of these areas was automatically calculated with ImageJ and represents the average of red, green, and blue color values (RGB) of the analyzed area, expressed in optical units per surface area.…”