Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels

TY - JOUR

T1 - Chemo-nociceptive signalling from the colon is enhanced by mild colitis and blocked by inhibition of transient receptor potential ankyrin 1 channels

AU - Mitrovic, Martina

AU - Shahbazian, Anaid

AU - Bock, Elisabeth

AU - Pabst, Maria A

AU - Holzer, Peter

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Background and purpose: Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified by mild colitis, morphine or a TRPA1 channel blocker. Experimental approach: One hour after intracolonic administration of AITC to female mice, afferent signalling was visualized by expression of c-Fos in laminae I-IIo of the spinal dorsal horn at sacral segment S1. Mild colitis was induced by dextran sulphate sodium (DSS) added to drinking water for 1 week. Key results: Relative to vehicle, AITC (2%) increased expression of c-Fos in the spinal cord. Following induction of mild colitis by DSS (2%), spinal c-Fos responses to AITC, but not vehicle, were augmented by 41%. Colonic inflammation was present (increased myeloperoxidase content and disease activity score), whereas colonic histology, locomotion, feeding and drinking remained unchanged. Morphine (10 mg·kg-1) or the TRPA1 channel blocker HC-030031 (300 mg·kg-1) inhibited the spinal c-Fos response to AITC, in control and DSS-pretreated animals, whereas the response to intracolonic capsaicin (5%) was blocked by morphine but not HC-030031. Conclusions and implications: Activation of colonic TRPA1 channels is signalled to the spinal cord. Mild colitis enhanced this afferent input that, as it is sensitive to morphine, is most likely of a chemonociceptive nature. As several irritant chemicals can be present in chyme, TRPA1 channels may mediate several gastrointestinal pain conditions.

AB - Background and purpose: Transient receptor potential ankyrin 1 (TRPA1) channels are expressed by primary afferent neurones and activated by irritant chemicals including allyl isothiocyanate (AITC). Here we investigated whether intracolonic AITC causes afferent input to the spinal cord and whether this response is modified by mild colitis, morphine or a TRPA1 channel blocker. Experimental approach: One hour after intracolonic administration of AITC to female mice, afferent signalling was visualized by expression of c-Fos in laminae I-IIo of the spinal dorsal horn at sacral segment S1. Mild colitis was induced by dextran sulphate sodium (DSS) added to drinking water for 1 week. Key results: Relative to vehicle, AITC (2%) increased expression of c-Fos in the spinal cord. Following induction of mild colitis by DSS (2%), spinal c-Fos responses to AITC, but not vehicle, were augmented by 41%. Colonic inflammation was present (increased myeloperoxidase content and disease activity score), whereas colonic histology, locomotion, feeding and drinking remained unchanged. Morphine (10 mg·kg-1) or the TRPA1 channel blocker HC-030031 (300 mg·kg-1) inhibited the spinal c-Fos response to AITC, in control and DSS-pretreated animals, whereas the response to intracolonic capsaicin (5%) was blocked by morphine but not HC-030031. Conclusions and implications: Activation of colonic TRPA1 channels is signalled to the spinal cord. Mild colitis enhanced this afferent input that, as it is sensitive to morphine, is most likely of a chemonociceptive nature. As several irritant chemicals can be present in chyme, TRPA1 channels may mediate several gastrointestinal pain conditions.

KW - Acetanilides

KW - Animals

KW - Capsaicin

KW - Colitis

KW - Colon

KW - Dextran Sulfate

KW - Disease Models, Animal

KW - Female

KW - Gene Expression Regulation

KW - Isothiocyanates

KW - Mice

KW - Morphine

KW - Neurons, Afferent

KW - Proto-Oncogene Proteins c-fos

KW - Purines

KW - Signal Transduction

KW - Transient Receptor Potential Channels

U2 - 10.1111/j.1476-5381.2010.00794.x

DO - 10.1111/j.1476-5381.2010.00794.x

M3 - Journal article

C2 - 20590633

SN - 0007-1188

VL - 160

SP - 1430

EP - 1442

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

IS - 6

ER -