Open Access(601) Preprotachykinin (PPT) mRNA and Substance P Receptor (NK1) mRNA Are Co‐Localized in Rat Dorsal Horn Neurons
Author(s) -
Alan Kahn
Publication year - 2000
Publication title -
pain medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.893
H-Index - 97
eISSN - 1526-4637
pISSN - 1526-2375
DOI - 10.1046/j.1526-4637.2000.000024-2.x
Subject(s) - substance p , messenger rna , dorsum , french horn , receptor , chemistry , medicine , endocrinology , anatomy , neuropeptide , gene , biochemistry , psychology , pedagogy
Aim of Investigation: To identify peptide receptors which may modulate transmission of nociceptive responses in second order pain afferents in the dorsal horn of the spinal cord. Substance P (SP), in addition to being synthesized by primary afferents, is also synthesized by dorsal horn neurons, many of which project to thalamic pain centers. 1 Double‐label in situ hybridization (ISH) techniques were used to determine if tachykinin and/or opioid receptors are expressed in these SP neurons. Methods: Spinal cord sections from Sprague‐Dawley rats were processed for ISH using digoxigenin‐labeled probes antisense to the mRNA coding for preprotachykinin (PPT, precursor to SP) combined with 33P‐labeled probes antisense to the mRNA coding for either the substance P receptor, NK1, or the mu opioid receptor, MOR1. Sections were examined for the presence of cells containing hybridization signal associated with digoxigenin‐labeled PPT probe co‐localized with hybridization signal associated with 33P‐labeled NK1 or MOR1 probe. Results: In lamina I of the dorsal horn greater than 50% of PPT‐positive cells were also positive for NK1, but in deeper laminae only 10% of PPT cells expressed NK1. No PPT‐positive cells contained MOR1 mRNA. Conclusions: These results demonstrate that a majority of SP synthesizing neurons in the dorsal horn, which are known to project to the thalamus and thus represent second order nociceptive neurons, also synthesize NK1 receptors. These data suggest possible circuits for modulating pain input: (1) a disynaptic SPergic pathway transmitting nociceptive information from the periphery to the thalamus and (2) a dorsal horn feedback circuit comprised of intrinsic SP neurons projecting back upon themselves or upon neighboring SP neurons. The absence of MOR1 co‐localized with intrinsic SP cells indicates that mu mu receptor influences on this circuit, if present, are indirect. J Comp Neurol 1992;315:473–486.