Analgesia in Amphibians: Preclinical Studies and Clinical Applications

Abstract

SYNOPSISPreclinical studies of analgesia in amphibians or recommendations for clinical use of analgesics in amphibian species are extremely limited. This article briefly reviews the issues surrounding the use of analgesics in amphibians starting with common definitions of pain and analgesia when applied to non-human animals. Nociceptive and endogenous opioid systems in amphibians are reviewed and results of preclinical research on opioid and non-opioid analgesics summarized. Recommended opioid and non-opioid analgesics are summarized and practical recommendations made for their clinical use. Keywords analgesia; amphibians; opioid; acetic acid test; Rana pipiens INTRODUCTIONAnalgesia is the selective loss of pain sensation leaving other cognitive, sensory and motor functions intact and ideally, unaltered. General anesthesia is the loss of all sensory and motor function, and a total lack of consciousness and awareness. Both analgesia and anesthesia are defined by description of these states in humans; it is at best an educated guess whether these definitions can also be applied accurately to non-human animals, or amphibians. Comparative neurology suggests that the potential for pain is less substantial in amphibians and other earlier-evolved vertebrates compared to humans. [1][2][3][4] There are very limited studies on either analgesia or anesthesia in amphibian species and only a few agents are recommended for clinical use. Anesthesia studies can be done to determine appropriate pharmacological agents and dosages by assessing simple measures like ability of an animal to right itself or to withdrawal its limb from a strong forceps pinch [5][6][7][8][9] but such studies will not be considered further here. In contrast, studies of analgesia are more difficult in amphibians as a validated assay is needed in which the animal exhibits a specific behavior in response to a potentially painful stimulus and in which that response is © 2010 Elsevier Inc. All rights reserved.Corresponding author: Craig W. Stevens, Ph.D., OSU-Center for Health Sciences, 1111 W. 17 th Street, Tulsa, OK 74107, 918.561.8234 (ph.), 918.561.8276 (fax), cw.stevens@okstate.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.The author has nothing to disclose. NIH Public Access Author ManuscriptVet Clin North Am Exot Anim Pract. Author manuscript; available in PMC 2012 January 1. reduced by a potential analgesic agent. A well-validated alternative pain and analgesia model using Rana pipiens has been in use for over twenty-five years, 10,11 however, in general, studies of analgesia in any non-mammalian species...

Propofol (2,6‐diisopropylphenol) is an applicable immersion anesthetic in the axolotl with potential uses in hemodynamic and neurophysiological experiments

“…Propofol is a sedative/hypnotic agent and is not considered analgesic. Overall very little is known about analgesics in amphibians (Stevens, ). If using propofol to induce anesthesia during more invasive procedures, additional analgesics may be considered.…”

Immersion and branchial/transcutaneous irrigation anaesthesia with alfaxalone in a Mexican axolotl

“…However, despite the apparently low dose administered in this case the axolotl appeared to return to normal activity, food consumption and behaviour rapidly. Failure to administer adequate analgesia during surgery has been associated with delayed return of these functions (Stevens 2011). It is interesting to note that higher doses reported would require the administration of extremely large relative volumes of drug using clinically available formulations of buprenorphine (0.3 mg kg )1 ) which seems both impractical and inappropriate (50 mg kg )1 in the axolotl reported would be a volume of 9.33 mL).…”

Advances in Amphibian Clinical Therapeutics

“…In amphibians, responses to multiple noxious stimuli were mitigated with administration of morphine, and this effect was reversible with naloxone. 19 Morphine (30 to 100 mg/kg IM, SC, or topical) provides analgesia that peaks at 60 to 90 minutes, with minimal reported adverse effects in leopard frogs (Rana pipiens). The seemingly high doses of morphine administered to frogs have not been associated with depression of neurological function.…”