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VOLUME 6, NUMBER 4
Analgesia, Vol. 6, pp. 499-505
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Reduction in OFQ/N1-17-Induced Analgesia Elicited From the Amygdala by Pretreatment With Mu, Kappa, and Delta Opioid Antagonists in Rats
Randi Shane, Jennifer Wolkin, and Richard J. Bodnar
Neuropsychology Doctoral Sub-Program and Department of Psychology, Queens College, City University of New York
The heptadecapeptide, orphanin FQ/nociceptin (OFQ/N1-17) binds with high affinity to the ORL-1/KOR-3 opioid receptor, but binds poorly with classic opioid receptors. Although it displays both hyperalgesic and analgesic responses following ventricular administration, OFQ/N1-17 only produces analgesia following administration into the amygdala. The present study examined whether amygdala pretreatment with equimolar (0.27-2.7 nmol) doses of either general (naltrexone), m (b-funaltrexamine), k (nor-binaltorphamine), or d (naltrindole) opioid receptor antagonists would alter OFQ/N1-17-induced analgesia elicited from the amygdala as measured by the tail flick test in rats. OFQ/N1-17 produced a modest analgesia across a 60-min time course that was significantly reduced by pretreatment with either general, m, k, or d opioid antagonists. Given that the amygdala, and particularly the medial amygdaloid nucleus, is a common site at which dense distributions of the ORL-1/KOR-3 receptor are found together with dense distributions of classic m, k, and d opioid receptors, these data suggest physiological interactions in the amygdala between neurons with classic opioid receptors and neurons with the ORL-1/KOR-3 receptor in mediating OFQ/N1-17-induced analgesia in the amygdala.
Key words: Amygdala; Analgesia; Orphanin FQ/Nociceptin; ORL-1/KOR-3 receptor; Mu receptor; Kappa receptor; Delta receptor
Address correspondence and reprint requests to Dr. Richard J. Bodnar, Department of Psychology, Queens College, CUNY, 65-30 Kissena Blvd., Flushing, NY 11367. Tel: (718) 997-3543; Fax: (718) 997-3257; E-mail: firstname.lastname@example.org
Preemptive Administration of Systemic Lidocaine Does Not Prevent Hyperalgesia in the Rat Chronic Constriction Injury Model of Neuropathic Pain
Lesley J. Smith,1 Andre Shih,1 and Vjekoslav Miletic2
1Department of Surgical Sciences, and 2Department of Comparative Biosciences, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706
Background: Systemic lidocaine can provide relief from many chronic
pain syndromes, including neuropathic pain. In a previous study we reported
that subcutaneous lidocaine administration at 0.67 or 1.3 mg/kg/h prevented
the development of thermal hyperalgesia (as a sign of neuropathic pain)
in rats following loose ligation of the sciatic nerve (i.e., chronic constriction
injury). In contrast, animals receiving saline or subcutaneous lidocaine
at 0.15 or 0.33 mg/kg/h exhibited hyperalgesia after sciatic nerve ligation.
Purpose: Based on these results, we hypothesized that lidocaine, when administered at a low dose continuously during the initial phase of the development of thermal hyperalgesia, might permanently prevent the development of full hyperalgesia even after lidocaine administration was terminated.
Methods: Saline or lidocaine was administered via subcutaneously implanted pumps for 24 h prior to loose sciatic ligation in male Sprague-Dawley rats (300 g). Three days after ligation the pumps were removed. Thermal hyperalgesia was assessed at baseline (presurgery), and 3, 5, and 7 days after sciatic ligation.
Results: Lidocaine prevented the development of hyperalgesia during continuous systemic administration through the first 3 days after surgery. Following removal of the lidocaine pumps the magnitude of hyperalgesia was diminished, despite nondetectable plasma lidocaine concentrations, on day 5. However, by day 7 thermal hyperalgesia was pronounced and not different from that in rats that had received saline.
Conclusions: Lidocaine provides antihyperalgesia in a neuropathic pain model during continuous systemic administration. Administration of lidocaine only during the development of the neuropathic state temporarily diminishes the magnitude of hyperalgesia even when lidocaine is no longer present.
Key words: Lidocaine; Hyperalgesia; Neuropathic pain; Chronic constriction injury model
Address correspondence and reprint requests to Lesley J. Smith, D.V.M., Department of Surgical Sciences, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706. Tel: (608) 265-9181; Fax: (608) 263-7930; E-mail: email@example.com
The Effect of Gabapentin on Carrageenan-Induced Hyperalgesia in Rats
Harry J. Gould, III,1 Trevor N. Gould,1 Lerna Minor,1 and Dennis Paul2
Departments of 1Neurology and 2Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA
Background. Our laboratory previously reported that gabapentin
produced no significant analgesic effect when used to treat thermal hyperalgesia
induced by complete Freund's adjuvant (CFA). This conclusion is an apparent
contradiction, to the observations of Field et al., who demonstrated that
gabapentin did produce an analgesic effect in treating thermal and mechanical
hyperalgesia following carrageenan-induced inflammation.
Purpose. The effect of gabapentin on inflammatory hyperalgesia induced by carrageenan was studied in rats and compared to the effects of gabapentin on complete Freund's adjuvant-induced hyperalgesia in order to clarify this discrepancy.
Methods. Paw withdrawal thresholds from both low- and high-intensity thermal stimuli and mechanical stimuli were measured at selected intervals following subcutaneous injections of either carrageenan or complete Freund's adjuvant in groups of rats that received gabapentin or normal saline prior to injection.
Results. Treatment with gabapentin produces a mild analgesic effect at 3 h after carrageenan injection, when tested with low-intensity thermal stimuli, but not with high-intensity thermal or with mechanical stimulation. Gabapentin did not increase paw withdrawal latencies associated with either low- or high-intensity thermal stimulation or mechanical stimulation following complete Freund's adjuvant administration.
Conclusions. Gabapentin has only a minimal analgesic effect in reducing pain associated with inflammation, and that effect is restricted to specific inflammatory conditions. In addition, we emphasize the importance of defining the stimulation parameters used in standard experimental models.
Key words: Gabapentin; Inflammation; Pain; Carrageenan; Hyperalgesia
Address correspondence and reprint requests to Harry J. Gould, III, M.D., Ph.D., Department of Neurology, LSU Health Sciences Center, 533 Bolivar Street, New Orleans, LA 70112. Tel: (504) 568-8171; Fax: (504) 568-7130; E-mail: firstname.lastname@example.org