Abstract
The presence of transient receptor potential vanilloid type-1 receptor (TRPV1)-like immunoreactivity (LI), in the form of nerve fibres and terminals, is shown in a set of discrete gray matter subregions placed in the territory of the human cuneate nucleus. We showed previously that those subregions share neurochemical and structural features with the protopathic nuclei and, after the ancient name of our town, collectively call them Locus Karalis, and briefly Locus K. TRPV1-LI in the Locus K is codistributed, though not perfectly overlapped, with that of the neuropeptides calcitonin gene-related peptide and substance P, the topography of the elements immunoreactive to the three markers, in relation to each other, reflecting that previously described in the caudal spinal trigeminal nucleus. Myelin stainings show that myelinated fibres, abundant in the cuneate, gracile and trigeminal magnocellular nuclei, are scarce in the Locus K as in the trigeminal substantia gelatinosa. Morphometric analysis shows that cell size and density of Locus K neurons are consistent with those of the trigeminal substantia gelatinosa and significantly different from those of the magnocellular trigeminal, solitary and dorsal column nuclei. We propose that Locus K is a special component of the human dorsal column nuclei. Its functional role remains to be determined, but TRPV1 appears to play a part in it.
Highlights
The transient receptor potential vanilloid type-1 receptor (TRPV1) is a polymodal ion channel expressed in primary sensory neurons, critically involved in the perception of mechanical and thermal stimuli as well as in pain modulation, and in allodynia and hyperalgesia in neuropathic pain [1,2,3,4,5,6,7].Temperature, low extracellular pH and capsaicin represent TRPV1 activators often used in experimental studies
TRPV1 is viewed as a molecular integrator of different stimuli in the peripheral polymodal nociceptors; it is activated by noxious heat, acidic and basic pH, voltage, endogenous lipid-derived compounds, and a variety of substances, among which the agonist resiniferatoxin is the best known [1,2,4,8,9,10,11]
Extending early observations on the presence of gray matter areas that are strongly immunoreactive to Substance P (SP) in the territory of the human cuneate nucleus and adjacent fascicle [70,71], we have shown that the cuneate nucleus fields rich in SP host neural structures immunoreactive to the neuropeptides CGRP, methionine- and leucine-enkephalin, peptide histidine-isoleucine, somatostatin and galanin, the trophin glial cell line-derived neurotrophic factor, and the neuroplasticity proteins polysialylated neural cell adhesion molecule and growth-associated protein-43 [92] and references therein
Summary
The transient receptor potential vanilloid type-1 receptor (TRPV1) is a polymodal ion channel expressed in primary sensory neurons, critically involved in the perception of mechanical and thermal stimuli as well as in pain modulation, and in allodynia and hyperalgesia in neuropathic pain [1,2,3,4,5,6,7]. Temperature (over 42 ◦ C), low extracellular pH and capsaicin represent TRPV1 activators often used in experimental studies. TRPV1 is viewed as a molecular integrator of different stimuli in the peripheral polymodal nociceptors; it is activated by noxious heat, acidic and basic pH, voltage, endogenous lipid-derived compounds, and a variety of substances, among which the agonist resiniferatoxin is the best known [1,2,4,8,9,10,11].
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