Recently studies have suggested that the TRPV1 receptor is involved in the visceral hypersensitivity response [
18,
19]. However, our current study demonstrates that elimination of the TRPV1 receptor expressing neurons does not alter the visceral hypersensitivity response to colorectal distension (CRD). It is important to note that our study looks at visceral hypersensitivity 14 days following inflammation. Some studies looking at visceral hypersensitivity have only studied this effect using acute inflammatory agents that do not last longer than 8 days [
29‐
31]. Conversely, Miranda et al. [
32] demonstrated that application of a TRPV1 antagonist (JYL1421) 14 days following TNBS inflammation resulted in an attenuation of the visceral motor response (VMR) as compared to the TNBS-only group. However, the response was still present as compared to control responses. Thus, the data suggest that blocking the TRPV1 receptor does result in a decrease in visceral hypersensitivity but does not eliminate the response entirely. The authors hypothesized that TRPV1 may be involved in the initial inflammation response and hypersensitivity but not the maintenance of the response. Another study has implicated the TRPV1 receptor in motility. De Schepper et al. [
33] used
In-Vivo techniques in conjunction with capsazepine, a TRPV1 antagonist, to demonstrate that the sensitization of the TRPV1 receptor inhibits colitis-induced abnormal motility patterns. Therefore, it is plausible that the TRPV1 receptor is involved in an extrinsic reflex pathway modulating motility patterns during a state of inflammation. It has also been shown that this abnormal motility reflex was eliminated following ligation of the pelvic nerve [
34]. In addition, Jones, III et al. [
19] demonstrated that the TRPV1 receptor may be involved in non-inflammatory visceral hypersensitivity using a TRPV1 knock-out model. The authors demonstrated that TRPV1 -/- mice receiving zymosan and CRD did not show an increase in the VMR response; however, matched controls did have an increase in the VMR response. In this model zymosan did not induce inflammation, as shown by an MPO assay, which is in contrast with studies done in rats showing that zymosan causes inflammation [
29]. Thus, our data in conjunction with the studies mentioned above suggest that the TRPV1 receptor may be involved in the mechanical component of the colonic inflammatory response but may not be the major component to maintaining visceral hypersensitivity.
Furthermore, it is important to note that the present study only looks at the involvement of the lumbosacral region of the spinal cord and its role in visceral hypersensitivity. Other studies have implicated the thoracolumbar region of the spinal cord in the mediation of the visceral hypersensitivity response [
20‐
23,
23]. Traub et al. [
20] demonstrated that both lumbosacral and thoracolumbar regions of the spinal cord were activated during CRD as shown by cFos and cJun labeling. However, the sacral region of the spinal cord had a higher cFos and cJun response to CRD (80 mmHg) compared to the thoracic region. A later study indicated that there is a differential involvement of the two regions of the spinal cord following CRD [
23]. To date, studies have not shown what receptors are involved in thoracolumbar mediation of visceral hypersensitivity and the exact role of this region in visceral hypersensitivity has yet to be determined. In the current study, we have shown that RTX lesions TRPV1 expressing DRG neurons in the thoracolumbar region in addition to the lumbosacral region following an intrathecal injection at the L6/S1 region of spinal cord and an intracolonic injection. Therefore, if the thoracolumbar DRG neurons are involved in visceral hypersensitivity, the present study demonstrates that the TRPV1 expressing neurons are not necessary to mediate visceral hypersensitivity.