Adenosine Receptor Agonists Modulate Visceral Hyperalgesia in the Rat

Abstract

Background/Aims: Adenosine is an endogenous modulator of nociception. Its role in visceral nociception, particularly in visceral hyperalgesia, has not been studied. The aim of this study was to determine the effects of adenosine receptor agonists in a model of visceral hyperalgesia. Methods: The visceromotor response (VMR) in rats to colorectal distension (CRD; 80 mmHg, 20 seconds) was quantified by electromyographic recordings from the abdominal musculature. Three hours after the intracolonic administration of zymosan (25 mg/mL, 1 mL), VMRs to CRD were measured before and after either subcutaneous or intrathecal administration of an adenosine receptor agonist. Results: Subcutaneous injection of 5'-N-ethylcarboxyamidoadenosine (NECA; an A1 and A2 receptor agonist), R(-)-N6-(2-phenylisopropyl)-adenosine (R-PIA; a selective A1 receptor agonist), or CGS-21680 hydrochloride (a selective A2a receptor agonist) dose-dependently (10-100 mg/kg) attenuated the VMR to CRD, although hindlimb weakness occurred at the higher doses tested. Intrathecal administration of NECA or R-PIA dose-dependently (0.1-1.0μg/kg) decreased the VMR, whereas CGS-21680 hydrochloride was ineffective over the same concentration range. Higher intrathecal doses of the A1/A2 receptor agonist NECA produced motor weakness. Conclusions: Adenosine receptor agonists are antihyperalgesic, but also produce motor weakness at high doses. However, activation of the spinal A1 receptor significantly attenuates the VMR to CRD without producing motor weakness. (Gut and Liver 2008;2:39-46)

P2X3 receptor‐mediated visceral hyperalgesia and neuronal sensitization following exposure to PTSD‐like stress in the dorsal root ganglia of rats

“…In brief, the rats were deeply anesthetized with 45 mg/kg sodium pentobarbital, administered ip . Electromyogram electrodes made by teflon‐coated stainless steel wire (Cooner Wire, Chatsworth, CA, USA) were implanted into the external oblique musculature, just superior to the inguinal ligament for EMG recordings as previously described …”

“…Electromyogram electrodes made by teflon-coated stainless steel wire (Cooner Wire, Chatsworth, CA, USA) were implanted into the external oblique musculature, just superior to the inguinal ligament for EMG recordings as previously described. [38][39][40] The electrode leads were then tunneled subcutaneously and externalized laterally through the skin of the abdomen and neck for future access. The incisions were closed with wound clips.…”

“…Visceral sensitivity was measured by grading behavioral response to phasic CRD as previously described, [40][41][42] before initiation of SPS (on day 0, as baseline), and at various time points (on days 1,6,7,14,21) in rats exposed to SPS. Briefly, after overnight fasting, the rats were anesthetized using isoflurane (3.0%) inhalation.…”

Inflammatory Bowel Diseases: It's Time for the Adenosine System

“…Pre-clinical studies pointed out an inhibitory effect exerted by adenosine, via A 1 receptor activation, on pain transmission both at pre-synaptic level, counteracting the pain-associated neurotransmitter release, such as glutamate, calcitonin gene-related peptide and substance P, and at post-synaptic level, through membrane cell hyperpolarization (68,69). Sohn et al reported that the intrathecal administration of the A 1 receptor agonist R-PIA, but not the A 2A receptor agonist CGS-21680 hydrochloride, decreased the visceromotor responses (70). Currently, some authors paid greater attention to the potential anti-nociceptive effects of A 3 agonists (71,72).…”

The Effects of 5-HT4 Receptor Agonist, Mosapride Citrate, on Visceral Hypersensitivity in a Rat Model

“…Several neurotransmitters may play an important role in the pathogenesis of motor abnormality and visceral hypersensitivity. Therefore, there is ongoing research on these neurotransmitters and on the development of new therapeutic targets [5]. 5-Hydroxytryptamine (5-HT, serotonin) is a modulator of gastrointestinal functions, including motility, secretion, and sensation, and is produced mainly in the enterochromaffin cells [6].…”