Inflammatory pain alters colorectal motility via spinal oxytocinergic pathways

Gastrointestinal motility is regulated primarily by the enteric and the central nervous systems. Our previous studies revealed that central circuits regulating colorectal motility partially overlap with those involved in pain modulation, suggesting functional interactions between the nociceptive modulatory pathway and the autonomic regulatory pathway of colorectal motility. Here, we examined whether peripheral inflammatory pain alters the neural components of the descending pathway regulating colorectal motility. Complete Freund's adjuvant (CFA) was administered unilaterally into the hind paw of rats to induce inflammation. Colorectal motility was assessed in vivo under anesthesia with α-chloralose and ketamine. In sham-treated rats, intraluminal administration of capsaicin, a noxious stimulus to the colorectal lumen, enhanced colorectal motility. In contrast, the capsaicin-induced colorectal motility response was suppressed in rats 3 days after CFA treatment. This suppression was rescued by the intrathecal administration of a GABA_A receptor antagonist or an oxytocin (OXT) receptor antagonist. Furthermore, spinal OXT administration and chemogenetic activation of OXT neurons in naïve rats elicited a marked inhibition of capsaicin-induced motility responses of the colorectum. Notably, the inhibitory effect of activated OXT neurons was abolished by the intrathecal administration of a GABA_A receptor antagonist. These results indicate that the descending OXT pathway becomes operative in response to persistent pain caused by peripheral inflammation and that the inhibitory effect on colorectal motility may involve local GABAergic transmission within the spinal cord. These changes may reduce parasympathetic outflow to the colorectum and contribute to defecation disorders involving central neural mechanisms.NEW & NOTEWORTHY This study focused on the remodeling of the neural pathways regulating colorectal motility and examined whether peripheral inflammation outside the gastrointestinal tract affects this process. In rats administered a complete Freund's adjuvant into their hind paw, colorectal motility responses induced by intracolonic administration of capsaicin were suppressed. This suppression involved oxytocinergic and GABAergic transmission in the spinal cord. These results demonstrate that inflammatory pain in the hind paw induces remodeling of the neural pathways regulating colorectal motility.