Centrally acting agents and visceral sensitivity

Abstract

The evidence relating to the site and mechanism of action of "centrally acting" agents which may affect visceral sensitivity is reviewed. Antidepressant drugs such as amitriptyline as well as the newer selective serotonin reuptake inhibitors are thought to act at the level of the CNS. Opiates, including morphine as well as compounds such as trimebutine or fedotozine designed for therapeutic use in irritable bowel syndrome, are effective in reducing visceral nociception. Cytokines in the CNS are known to be involved in the modulation of pain and there is also evidence to suggest that centrally acting cytokines may play a role in the production of visceral hypersensitivity. Consequently, they may provide an interesting target for future research.

Figure 1

(A) A 21 day treatment with amitriptyline in healthy volunteers increased cutaneous electrical current to induce moderate pain. *p<0.05. Modified from Gorelick and colleagues.²⁰ (B) Amitriptyline did not significantly modify perception, discomfort, or pain thresholds to rectal distension. Modified from Gorelick and colleagues.²⁰

Figure 2

Comparative antinociceptive action of loperamide (A) and morphine (B) in reducing writhing induced by intraperitoneal acetic acid in mice. Loperamide, which poorly crosses the blood-brain barrier displays a potency similar to that of morphine. The selective peripheral opiate receptor antagonist, quaternary naltrexone, similarly antagonises the effects of loperamide and morphine. These data suggest a peripheral action of opiates in reducing pain induced by peritoneal irritation. Modified from Takasuna and colleagues.⁴⁶

Figure 3

Role of central human recombinant interleukin 1ß (rhIL-1ß) in allodynia to rectal distension (0.4 ml) induced by lipopolysaccharide (LPS). LPS administered intraperitoneally (ip) induced delayed allodynia at 3, 9, and 12 hours after administration. Similarly, allodynia appeared 9 and 12 hours after intracerebroventricular (icv) administration of IL-1ß. Modified from Coelho and colleagues.^66,67