TPRV1 expression defines functionally distinct pelvic colon afferents.
Changes in primary sensory neurons are likely to contribute to the emergence of chronic visceral pain. An important step in understanding visceral pain is the development of comprehensive phenotypes that combines functional and anatomical properties for these neurons. We developed a novel ex vivo physiology preparation in mice that allows intracellular recording from colon sensory neurons during colon distension, in the presence and absence of pharmacologic agents. This preparation also allows recovery of functionally characterized afferents for histochemical analysis. Recordings obtained from L6 dorsal root ganglion cells in C57BL/6 mice identified two distinct populations of distension-responsive colon afferents: high-firing frequency (HF) and low-firing frequency (LF) cells. Fluid distension of the colon elicited rapid firing (>20 Hz) in HF cells, whereas LF cells seldom fired >5 Hz. Distension response thresholds were significantly lower in HF cells (LF, 17.5 +/- 1.1 cmH(2)O; HF, 2.6 +/- 1.0 cmH(2)O). Responses of most LF afferents to colon distension were sensitized by luminal application of capsaicin (1 microm; 8 of 9 LF cells), mustard oil (100 microm; 10 of 12 LF cells), and low pH (pH 4.0; 5 of 6 LF cells). In contrast, few HF afferents were sensitized by capsaicin (3 of 9), mustard oil (2 of 7), or low pH (1 of 6) application. Few HF afferents (4 of 23) expressed the capsaicin receptor, TRPV1. In contrast, 87% (25 of 29) of LF afferents expressed TRPV1. TRPV1 has been shown to be required for development of inflammatory hyperalgesia. These results suggest a unique functional role of TRPV1-positive colon afferents that could be exploited to design specific therapies for visceral hypersensitivity.
Malin
Sacha A
SA
Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Christianson
Julie A
JA
Bielefeldt
Klaus
K
Davis
Brian M
BM
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001703:Biophysics; D002211:Capsaicin / Q000494:pharmacology; D003106:Colon / Q000166:cytology* / Q000294:innervation; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009149:Mustard Plant; D017288:Pain Threshold / Q000187:drug effects; D010388:Pelvis; D010812:Physical Stimulation / Q000379:methods; D010938:Plant Oils / Q000494:pharmacology; D011984:Sensory Receptor Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D018689:Sensory System Agents; D018709:Statistics, Nonparametric; D050916:TRPV Cation Channels / Q000378:metabolism*; D017833:Visceral Afferents / Q000502:physiology*
C494994:Gfra3 protein, mouse; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D010938:Plant Oils; D018689:Sensory System Agents; D050916:TRPV Cation Channels; D002211:Capsaicin; C027793:mustard oil