Attenuation of reperfusion hyperalgesia in the rat by systemic administration of benzodiazepines

Abstract

1 An investigation into whether reperfusion hyperalgesia is modulated by prior systemic administration of two benzodiazepine agonists (diazepam and chlordiazepoxide), and an antagonist (flumazenil) was conducted. 2 Transient ischaemia was induced in conscious rats by applying an inflatable tourniquet to the base of the tail; when the rats exhibited a co-ordinated escape response, the tourniquet was deflated and reperfusion of the tail was allowed. Reperfusion hyperalgesia manifested as a decrease in tail flick latency, following tail immersion in 49'C water, after the release of the tourniquet. 3 Intraperitoneal administration of diazepam, chlordiazepoxide and flumazenil had no effect on the co-ordinated escape to the noxious ischaemic stimulus nor on tail flick latency after application of a sham tourniquet. 4 The hyperalgesia evident during reperfusion, was abolished by diazepam (1 and 5 mg kg-') and chlordiazepoxide (5 and 25 mg kg-'). The antihyperalgesic effects of both diazepam (5 mg kg-') and chlordiazepoxide (25 mg kg-) were inhibited by flumazenil (1 mg kg-'). 5 Rotarod performance was impaired in rats given diazepam and chlordiazepoxide at the same doses at which the benzodiazepines were antihyperalgesic. The impairment to motor function did not extend to the motor systems involved in the tail flick response. 6 In conclusion, benzodiazepines have antinociceptive properties during hyperalgesia.

Effects of Benzodiazepines on Acute and Chronic Ethanol-Induced Nociception in Rats

“…In contrast, diazepam produced no antinociception on its own. This finding is comparable to earlier research in which benzodiazepines were reported to produce little or no antinociceptive effects as measured by tail-flick or activity of pain fibers (Cartmell and Mitchell, 1993;Jurna, 1984;Niv et al, 1983). Diazepam also failed to alter the antinociceptive effects of ethanol, although the sedative effects of the two compounds seem to have been compounded.…”

“…The GABA system is thought to prevent mild stimuli from eliciting pain responses (Yaksh and Malmberg, 1994). It is not surprising, then, that drugs which act at the GABAA receptor, such as the benzodiazepines, produce only a small amount of antinociception (Cahusac et al, 1984;Cartmell and Mitchell, 1993). Ethanol facilitates GABAA receptor activity through allosteric enhancement of agonist-induced receptor activation and may also enhance agonist-induced desensitization.…”

Interactions Between Metoclopramide and Morphine: Enhanced Antinociception and Motor Dysfunction in Rats

“…Finally, other studies have also shown that drug-induced impairment of motor performance on the rotarod does not compromise the tail-flick test. 40 Our ability to extrapolate our results to the clinical setting, where metoclopramide and morphine are typically administered to patients with pain lasting more than a few hours, may be compromised by our use of a model of acute pain and hyperalgesia. Because prolonged pain is associated with changes in the neural processing of nociceptive information, 41 the antinociceptive efficacy of morphine and metoclopramide may also change depending on the duration of the pain.…”

Comparative study of the sedative and antinociceptive effects of levomepromazine, azaperone and midazolam in laboratory animals

“…Although several studies have demonstrated benzodiazepines as analgesics, other studies have emphasized that this drug does not possess any antinociceptive property (Clavier et al, 1992). Cartmell and Mitchell (1993) demonstrated that benzodiazepines attenuate hyperalgesia in ischemia-reperfusion of the rat tail artery.…”