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INTRATHECAL CARBONIC ANHYDRASE INHIBITORS BLOCK HYPERALGESIA INDUCED IN RATS BY PENTOBARBITAL BUT NOT BY PROPOFOL

Department of Anesthesia, University of Calgary, Calgary, Canada T2N 2T9

INTRODUCTION

Systemic administration of barbiturates or propofol reduces nociceptive reflex latency (1). Systemic administration of the carbonic anhydrase inhibitor (CAI), acetazolamide, blocked nociceptive reflex enhancement by pentobarbital(2). Here we have examined the role of spinal carbonic anhydrase (CA) in the reduction of of nociceptive reflex latency by systemic administration of pentobarbital and propofol.

METHODS

Experimental protocols were approved by the Faculty of Medicine Animal Care Committee. Twenty male Sprague Dawley rats (300-500g) were instrumented with chronic indwelling intrathecal (i.t.)(3) catheters whose distal ports were situated in the lumbar region. The catheters were injected with 10 µl of artificial cerebrospinal fluid (aCSF), either drug-free or containing either 50 µM ethoxyzolamide or 20 µM acetazolamide. Fifteen minutes after i.t. drug injection, animals received an intraperitoneal injection of 30 mg/kg of pentobarbital or 50mg/kg of propofol. A blinded observer measured nociceptive reflex latency sequentially in the four limbs before and ten min after the i.t. CAI injection and then 5, 15, 25, 35, 45 and 55 min after the i.p. anesthetic injection. Nociceptive reflex latencies were normalized with respect to the pre-anesthetic values. Data was analyzed with paired t-tests.

RESULTS

The administration of pentobarbital or propofol reduced the paw withdrawal latency to 60-70% of control values in both fore-and hind-limbs. Intrathecal administration of CAI blocked reflex enhancement in the hindlimbs but not in the forelimbs. CAI injection did not block reflex enhancement by propofol in the hindlimbs.

TABLE

Treatment Group Nociceptive Reflex Latency, % of Control Values n Forelimbs Hindlimbs Pentobarbital i.p.     Ethoxyzolamide i.t. 8 62 ± 12 82 ± 9*     Acetazolamide i.t. 8 62 ± 11 94 ± 21* Propofol i.p.     Ethoxyzolamide i.t. 5 65 ± 6 68 ± 15     Acetazolamide i.t. 3 73 ± 4 75 ± 2 Mean values ± standard deviation * P <0.001 compared to forelimbs

DISCUSSION

Spinal carbonic anhydrase is involved in nociceptive reflex enhancement pentobarbital, but not by propofol. The neural mechanisms for nociceptive reflex enhancement may be different for these two drugs.

REFERENCES

1 Can J Anaesth 42, 532–40

2 Anesthesiology 90: 1158–64

3 Physiol Behav 7: 1032–6

4 Pain 32: 77–88

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