Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment

doi:10.1016/0006-8993(95)01094-7

Brain Research

Volume 703, Issues 1–2, 12 December 1995, Pages 175-183

https://doi.org/10.1016/0006-8993(95)01094-7 Get rights and content

Abstract

Vanilloid (capsaicin) receptors were visualized by [3H]resiniferatoxin (RTX) autoradiography in the brain of newborn as well as adult (both control and colchicine-treated) rats. Specific labelling was seen in the brain stem only, in the nucleus of the solitary tract extending into the area postrema and the spinal sensory nucleus of the trigeminal nerve. Also, a strong signal was seen in the dorsal horn, dorsal root, trigeminal and nodose ganglia. Membranes obtained from the cervical, thoracic, and lumbar segments of the spinal cord showed similar affinities for RTX and likewise for capsaicin and capsazepine; maximal receptor density was similar in the cervical and thoracic segments (approximately 70 fmol/mg protein) but was twice as high in the lumbar segment. 24 h after ligation of the vagal or the sciatic nerves, a strong accumulation of specific RTX binding sites was observed mainly proximal to the ligature, implying intraaxonal receptor transport from the nodose and dorsal root ganglia, respectively, to the periphery. Systemic (s.c.) vanilloid treatment depleted specific [³H]RTX binding sites from the brain stem, the sensory (dorsal root as well as trigeminal) ganglia, and the spinal cord. RTX was approximately 200-fold more potent than capsaicin for eliminating vanilloid receptors from the spinal cord. The present results suggest a discrete expression of vanilloid receptors in the brain stem (sensory nuclei); although intrinsic vanilloid receptor-expressing neurons are thought to exist in the rat brain, they remain undetected by the present [³H]RTX autoradiography methodology.

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The capsaicin receptor has been found and studied not only in the peripheral nervous system but also in the brain. Although there are conflicting reports about cerebral TRPV1 localization and expression ranging from a lack of receptor expression, or very restricted to widespread receptor expression in the central nervous system (CNS) [10,35,45,51], the neurobehavioral relevance of the receptor has been thoroughly analyzed and confirmed in several rodent studies. For instance, it has been shown that TRPV1 contributes to anxiety, fear, and panic-like responses in brain regions related to defensive responses such of those of the hippocampus, the periaqueductal gray (PAG), or the medial prefrontal cortex [6,18,32].
The transient receptor potential vanilloid receptor type–1 (TRPV1) is critically involved in peripheral nociceptive processes of somatic and visceral pain. However, the role of the capsaicin receptor in the brain regarding visceral pain remains elusive. Here, we studied the contribution of TRPV1 to abdominal pain transmission at different nociceptive pathway levels using TRPV1 knock-out mice, resiniferatoxin-mediated deletion of TRPV1-positive primary sensory neurons, and intracerebral TRPV1 antagonism. We found that constitutive genetic TRPV1 deletion or peripheral TRPV1 deletion reduced acetic acid–evoked abdominal constrictions, without affecting referred abdominal hyperalgesia or allodynia in an acute pancreatitis model of visceral pain. Notably, intracerebral TRPV1 antagonism by SB 366791 significantly reduced chemical and inflammatory spontaneous abdominal nocifensive responses, as observed by reduced expressions of nociceptive facial grimacing, illustrating the affective component of pain. In addition to the established role of cerebral TRPV1 in anxiety, fear, or emotional stress, we demonstrate here for the first time that TRPV1 in the brain modulates visceral nociception by interfering with the affective component of abdominal pain.

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Vanilloid (capsaicin) receptors in the rat: distribution in the brain, regional differences in the spinal cord, axonal transport to the periphery, and depletion by systemic vanilloid treatment

Abstract

Life Sci.

Life Sci.

Mol. Brain Res.

Neurosci. Lett.

Neuroscience

Brain Res.

Life Sci.

Brain Res.

Gen. Pharmacol.

Neuroscience

Brain Res.

Life Sci.

Brain Res.

Neurosci. Lett.

Life Sci.

Eur. J. Pharmacol.

Neuroscience

Capsazepine: a competitive antagonist of the sensory neurone excitant capsaicin

Br. J. Pharmacol.