Preemptive analgesia: a research review.

Current clinical research studying the administration of local anesthetics, opioids, and nonsteroidal anti-inflammatory agents prior to various types of surgery are reviewed. These agents can reduce pain and improve patient management in the postoperative period, but this technique can be controversial. Implications for nurses are discussed.

Toxicity of cocaine.

Abuse of central nervous system (CNS) stimulants continues to escalate within the United States. This group of powerful drugs includes cocaine, "crack" (free-base cocaine), methamphetamine, and "ice" (free-base methamphetamine). The pharmacological actions are similar among these agents, but their onsets and durations of action differ. Patients using and abusing cocaine and methamphetamines may present themselves as dental patients. It is therefore important for dental clinicians to understand the pharmacology of these drugs.

Effect of chronic treatment with tricyclic antidepressants upon antinociception induced by intrathecal injection of morphine and monoamines.

The effects of acute and chronic treatment with tricyclic antidepressants (TCA) upon antinociception induced by intrathecally administered serotonin (5-HT), norepinephrine (NE), and morphine were assessed at weekly intervals by the tail-flick method in the rat. Acute pretreatment with either clomipramine (28.5 mumol/kg, s.c.) or desipramine (85.5 mumol/kg, s.c.) enhanced the analgesia induced by both intrathecally-administered morphine (7.5 nmol) and 5-HT (241 nmol), compared to saline (1 ml/kg) but only desipramine facilitated the effects of intrathecally administered NE (0.49 nmol). The chronic (22 day) administration of both tricyclic antidepressants resulted in loss of the enhancement of the effects of morphine (day 22) and 5-HT (day 15); only desipramine (day 15) abolished the facilitation of NE. In a similar study, acute pretreatment with the non-tricyclic antidepressant inhibitor of the reuptake of NE, nisoxetine, (97.5 mumol/kg, s.c.), amplified the effects of intrathecally administered NE and morphine but not 5-HT-induced analgesia. Although chronic (22 day) treatment with nisoxetine caused a loss of the effects of enhancement of morphine (day 8), there was no effect upon the action of NE and antinociception induced by 5-HT was facilitated (day 22). Receptor binding studies indicated that chronic (22 day) treatment with clomipramine, desipramine or nisoxetine reduced the affinity of opiate [3H]naloxone) receptors in the spinal cord. These results demonstrate that (1) acute treatment with trycyclic antidepressants enhanced analgesia induced by intrathecally injected morphine, and (2) the chronic administration of trycyclic antidepressants resulted in a loss of enhancement of the effects of morphine, given intrathecally, which appeared to be independent of alterations in the activity of NE or 5-HT but may be associated with the development of subsensitive opiate receptors.

Effect of alpha 2 adrenergic agents upon central etorphine antinociception in the cat.

Systemic (s.c.) administration of alpha 2 agonists clonidine (25-100 micrograms/kg) or guanfacine (50-400 micrograms/kg) elicited antinociception as assessed by the cat tail-flick model and potentiated in a dose-dependent manner the antinociceptive effect of etorphine (2.5 micrograms) administered directly into the periaqueductal gray. Conversely, systemic yohimbine (1 mg/kg) attenuated the effects of central etorphine, and diminished potentiation of etorphine by the alpha 2 agonists. Prior microinjection of clonidine (5 micrograms) or guanfacine (5 micrograms) into the locus coeruleus (LC) reduced the intensity of central etorphine antinociception whereas central yohimbine (20 micrograms) pretreatment increased peak antinociceptive activity and prolonged the duration of etorphine. Thus, systemic alpha 2 agonists are inherently antinociceptive and potentiate central narcotic antinociception; however, the site of interaction between alpha 2 agonists and opiates does not appear to be the LC inasmuch as alpha 2 agonists attenuate the antinociceptive effect of etorphine when administered directly into the LC. A spinal site of action is suggested based upon known LC-spinal projections and our experimental observations.

Feline analgesia following central administration of opioids.

Activity of opioids in cats was assessed by employing the tail-flick method. Microinjection of morphine (100 micrograms) or etorphine (2.5 micrograms) into the ventrolateral periaqueductal gray (VLPAG) region resulted in significant analgesia. Smaller doses of morphine (10 and 50 micrograms) or etorphine (0.62 and 1.25 micrograms) were without significant effect. Methadone likewise produced no significant analgesic action in doses as large as 360 micrograms in the ventrolateral periaqueductal gray. Rank order potency, i.e. etorphine greater than morphine much greater than methadone, was similar following systemic administration. Increased latency of tail-flick response after injection of etorphine was diminished by administration of naloxone, either systemically or centrally, thus indicating a specific opiate-mediated response.

Augmentation of central and peripheral morphine analgesia by desipramine.

Using the rat tail-flick method to assess analgetic efficacy, the effects of desipramine (DMI) on analgesia produced by either systemic or central (i.e., periaqueductal gray) administration of morphine sulfate (MS) were evaluated. Pretreatment of rats with DMI (30 mg/kg, s.c.) increased the duration of analgesia following systemic injection of MS (5.0 mg/kg, s.c.) from 50 min to 150 min, but did not significantly alter the peak analgetic response. A similar but less marked effect was observed following a 2.5 mg/kg dose of MS. Pretreatment with DMI likewise extended the duration of effective analgesia following microinjection of 2.5 micrograms and 5.0 micrograms MS into the ventrolateral periaqueductal gray region (VLPAG). In addition, the maximal analgetic response to the 5.0 microgram dose of MS was increased by DMI. These results suggest that potentiation of morphine-induced analgesia by DMI cannot be ascribed solely to a peripheral interaction (i.e. inhibition of hepatic biotransformation) but probably involves a central interaction as well.

Differential effects of LSD serotonin and l-tryptophan on visually evoked responses.

Alterations in photically-evoked cortical responses were assessed in immobilized artificially respired cats following intraraphe microinjections of LSD and serotonin (5-HT) and IV administration of LSD and l-tryptophan. Both systemic (10-100 micrograms/kg; N = 5) and intraraphe (0.25 microgram; N = 10) LSD significantly increased the amplitudes of the three primary components of the visual evoked response (VER). In contrast, the same VER components were significantly depressed following intraraphe 5-HT (30 micrograms; N = 4) and IV l-tryptophan (100 mg/kg; N = 6), a serotonin precursor that elevates raphe 5-HT levels. Intraraphe cinanserin (180 micrograms; 30 minute pretreatment) completely reversed LSD-induced enhancements in all three components (p less than 0.01). Depressions of VER following intraraphe 5-HT (30 micrograms) were also antagonized by cinanserin, although to lesser degree (p less than 0.05 for first 2 components only) than with LSD. The depressive effects of l-tryptophan (100 mg/kg) were unaffected by cinanserin. Modification of raphe neuronal activity can significantly alter photically evoked responses, and may explain the perceptual disturbances associated with LSD, i.e., depression of an area (raphe) normally inhibiting forebrain areas of the visual system.