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The Journal of Neuroscience, January 21, 2009, 29(3):743-752; doi:10.1523/JNEUROSCI.3791-08.2009

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Neurobiology of Disease
TRPV1 Expression Defines Functionally Distinct Pelvic Colon Afferents

Sacha A. Malin,^1,3 Julie A. Christianson,^1,3 Klaus Bielefeldt,^1,3 and Brian M. Davis^1,2,3

¹Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, ²Department of Neurobiology, and ³Pittsburgh Center for Pain Research, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213

Correspondence should be addressed to Brian M. Davis, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, E1440 Basic Medical Science Tower, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261.

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 cmH₂O; HF, 2.6 ± 1.0 cmH₂O). Responses of most LF afferents to colon distension were sensitized by luminal application of capsaicin (1 µM; 8 of 9 LF cells), mustard oil (100 µM; 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.

Key words: visceral pain; TRPA1; capsaicin; mustard oil; nociceptor; inflammation

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Received Aug. 11, 2008; revised Oct. 3, 2008; accepted Nov. 18, 2008.

Correspondence should be addressed to Brian M. Davis, Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, E1440 Basic Medical Science Tower, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA 15261.

This article has been cited by other articles:

				D. J Levinthal and K. Bielefeldt Differences in post-inflammatory hypersensitivity between splanchnic and pelvic afferents: mechanisms and implications for human disease Gut, October 1, 2009; 58(10): 1317 - 1318. [Full Text] [PDF]

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