Evaluation of butorphanol tartrate and buprenorphine hydrochloride on the inflammatory reaction of the Sereny Test
Swearengen, J.R.; Cockman-Thomas, R.A.; Davis, J.A.; Weina, P.J.
Laboratory Animal Science 43(5): 471-475
1993
ISSN/ISBN: 0023-6764 PMID: 8277729 Document Number: 413508
Invasion of the ocular epithelia of guinea pigs by virulent Shigella organisms, eliciting keratoconjunctivitis, is the basis of the Sereny Test (ST). This test has been used to ascertain the virulence of Shigella strains and more recently to screen candidate Shigella vaccines for efficacy. This test undoubtedly causes pain in test animals; however, recommendation for use of local analgesics/anesthetics has not been accepted because of concern that thee topical agents may affect the ability of the Shigella organisms to invade the ocular epithelia or have a physiologic effect on the inflammatory process. Similarly, investigators are hesitant to use systemic analgesics in conjunction with the ST. Two blinded studies were conducted to evaluate the effects of selected systemic analgesics on the ST in outbred Hartley guinea pigs. Study 1 evaluated the recommended dosage for two systemic analgesics; study groups consisted of those receiving butorphanol tartrate (n = 16), those receiving buprenorphine hydrochloride (n = 16), and untreated controls (n = 5). Study 2 evaluated a low-dose buprenorphine hydrochloride group (n = 16) and an untreated control group (n = 5). All animals were inoculated with Shigella flexneri, strain 2a 2456T, onto the cornea and conjunctiva of each eye. At the onset of clinical signs, analgesics were administered to test groups. The degree of keratoconjunctivitis was evaluated per standard procedure; animals were weighed daily. After 7 days, animals were euthanized and the eyes were removed for histologic morphometric evaluation. Clinical observations of keratoconjunctivitis in both studies were not significantly different. Histologic morphometry confirmed clinical observations when each analgesic treatment group was compared with the corresponding untreated control group. Mean individual weight gains were less in all analgesic groups when compared with their untreated control group and were attributed to opioid-induced sedation. Our findings suggest that agonist-antagonist opioid analgesics do not interfere with the inflammatory response of the ST. Although heavy buildup of periorbital mucopurulent discharge in the buprenorphine study-1 group complicated clinical observations, the lower dose of buprenorphine (study 2) appears compatible for use with the ST, on the basis of non-interference with the inflammatory reaction, logistical advantages over butorphanol, and minimal interference with making clinical observations.