Gut Liver.  2008 Jun;2(1):39-46.

Adenosine Receptor Agonists Modulate Visceral Hyperalgesia in the Rat

• Sohn CI
• Park HJ
• Gebhart GF

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 (0.1-1.0 microgram/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.

Keyword

Adenosine; Visceral; Hyperalgesia

MeSH Terms

Adenosine
Adenosine-5'-(N-ethylcarboxamide)
Animals
Hindlimb
Hyperalgesia
Injections, Subcutaneous
Nociception
Purinergic P1 Receptor Agonists
Rats
Receptors, Purinergic P1
Zymosan
Adenosine
Adenosine-5'-(N-ethylcarboxamide)
Purinergic P1 Receptor Agonists
Receptors, Purinergic P1
Zymosan