Anthony L. Vaccarino

Endogenous opiates: 1998.

This paper is the twenty-first installment of our annual review of research concerning the opiate system. It summarizes papers published during 1998 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; eating and drinking; alcohol; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunologic responses; and other behaviors.

Endogenous opiates: 1999

This paper is the twenty-second installment of the annual review of research concerning the opiate system. It summarizes papers published during 1999 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunologic responses.

Endogenous opiates: 2000

This paper is the twenty-third installment of the annual review of research concerning the opiate system. It summarizes papers published during 2000 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; learning, memory, and reward; eating and drinking; alcohol and other drugs of abuse; sexual activity, pregnancy, and development; mental illness and mood; seizures and other neurological disorders; electrical-related activity; general activity and locomotion; gastrointestinal, renal, and hepatic function; cardiovascular responses; respiration and thermoregulation; and immunological responses.

Analgesic effects of endomorphin-1 and endomorphin-2 in the formalin test in mice.

Two recently isolated peptides, endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2), are highly selective micro-opioid receptor agonists with analgesic actions in the tail-flick test. To further assess the analgesic properties of these peptides, the effects of endomorphin-1, endomorphin-2, and morphine were examined in the formalin test. Male Swiss Webster mice were injected i.c.v. with endomorphin-1, endomorphin-2, or morphine (0, 1, 3, 10 microg) 5 min before injection of 20 microl of 5% formalin s.c. into the plantar surface of one hind-paw. The mice were observed for 60 min after formalin injection. Endomorphin-1 and endomorphin-2 produced dose-dependent analgesia that was shorter in duration than for morphine. Increased locomotion was observed after morphine, but not after endomorphin-1 or endomorphin-2. These findings extend previous results and suggest that endomorphins may have therapeutic potential for the treatment of acute pain.

Relationship between hypothalamic-pituitary-adrenal activity and blockade of tolerance to morphine analgesia by pain: a strain comparison

&NA; We previously reported that morphine fails to produce analgesic tolerance when administered in the presence of formalin‐induced pain. The hypothalamic‐pituitary‐adrenal (HPA) axis is known to respond to stressful stimuli, including pain. To examine whether the blockade of tolerance by pain is related to HPA activity, we assessed the development of tolerance to morphine analgesia in an inbred strain of rats that lack typical stress‐induced HPA responses (Lewis strain). Lewis rats lack typical stress‐induced activation of corticotropin‐releasing hormone, adrenocorticotropin hormone and glucocorticoids. Female Lewis rats were injected with morphine (20 mg/kg, i.p.) or saline for 4 consecutive days in the presence or absence of pain induced by injection of formalin into the hind‐paw. The analgesic effect of morphine (5, 10 or 20 mg/kg, i.p.) was then measured in the tail‐flick test 24 h after tolerance induction. Inbred female Fischer rats, which show significant stress‐induced HPA activity, were used for comparison. Analgesic tolerance was produced in both strains when morphine was delivered in the absence of pain. However, the presence of pain during morphine administration prevented the development of analgesic tolerance in Fischer, but not in Lewis, rats. The differential effects of pain on the development of tolerance to morphine analgesia are suggested to be related to genetically determined differences in stress‐induced HPA activity.

Morphine fails to produce tolerance when administered in the presence of formalin pain in rats

The present study examined the development of tolerance to morphine analgesia under conditions in which morphine was administered in the presence or absence of pain induced by subcutaneous injection of 50 microliters of 2.5% formalin into the hind paw of rats. Animals were injected with morphine (25 mg/kg, i.p.) or saline for 3 consecutive days either in the presence of pain (10 min after formalin injection) or in the absence of pain (6 h prior to formalin injection). On the 4th day, tolerance to the analgesic effect of test doses of morphine (6 or 10 mg/kg) was assessed in the formalin and tail-flick tests, respectively. Significant tolerance in both tests was observed in animals receiving morphine in the absence of pain during the tolerance induction period, but not in animals receiving morphine in the presence of pain.

Endogenous opiates: 1997.

This paper is the twentieth installment of our annual review of research concerning the opiate system. It summarizes papers published during 1997 that studied the behavioral effects of the opiate peptides and antagonists, excluding the purely analgesic effects, although stress-induced analgesia is included. The specific topics covered this year include stress; tolerance and dependence; eating and drinking; alcohol; gastrointestinal, renal, and hepatic function; mental illness and mood; learning, memory, and reward; cardiovascular responses; respiration and thermoregulation; seizures and other neurologic disorders; electrical-related activity; general activity and locomotion; sex, pregnancy, and development; immunologic responses; and other behaviors.

Injury prior to neurectomy alters the pattern of autotomy in rats. Behavioral evidence of central neural plasticity.

A common property of phantom limb pain is that a preamputation lesion continues to be felt in the same location of the phantom limb after amputation. A model of the phantom limb in the rat is provided by sectioning the sciatic and saphenous nerves. This procedure leads to self-mutilation of the denervated hindpaw, a behavior known as autotomy. There is strong evidence that autotomy is a response to painful or dysesthetic sensations referred to the anesthetic limb. The present study examined the hypothesis that the site of autotomy behavior can be altered by an injury given prior to denervation. Experiment 1 evaluated the effects of a thermal injury applied (under sodium pentobarbital anesthesia) to the medial or lateral hindpaw and digits before or after sciatic and saphenous nerve transections in order to determine whether autotomy is directed specifically to a previously injured site. The results revealed that autotomy onset occurred in the injured region of the paw in a significantly greater proportion of rats, compared to an uninjured control group, if the thermal injury had been induced before denervation: 100% of the rats with medial paw injury induced prior to neurectomy initiated autotomy in the medial digits, and 55.6% of rats with lateral paw injury initiated autotomy in the lateral digits. Rats injured after autotomy showed no such preference (medial, 33.3% and lateral, 37.5%) relative to the uninjured controls (medial, 33.3% and lateral, 17%). These results suggest that central cells, sensitized by the thermal injury, contribute to enhanced autotomy in the absence of further inputs from the injured paw.(ABSTRACT TRUNCATED AT 250 WORDS)

Descending modulation of central neural plasticity in the formalin pain test

Subcutaneous injection of formalin produces a biphasic profile of pain response: a transient early phase followed by a tonic late phase. A number of studies have indicated that the development of the late phase of formalin pain is dependent upon prolonged changes in central neural function produced by neural activity that is generated during the early phase (i.e. central sensitization). In support of this, the present demonstrates that stimulation- or morphine-produced analgesia derived from the periaqueductal grey (PAG) during the early phase prevents the development of the phase. These results suggest that descending mechanisms of pain inhibition, as reflected by PAG stimulation- and morphine-produced analgesia, can prevent the development of central neural plasticity following injury.

A role of periaqueductal grey NMDA receptors in mediating formalin-induced pain in the rat.

In the present study we examined the role of periaqueductal grey (PAG) N-methyl-D-aspartate (NMDA) receptors in the perception of tonic and phasic pain. Under sodium pentobarbital anesthesia rats were implanted unilaterally with a guide cannula aimed at the PAG. Following a 7-14 day recovery period rats received an infusion of the NMDA antagonist, 2-amino-5-phosponopentanoic acid (AP5), or saline into the PAG. Five minutes after the infusion of AP5 rats were tested for analgesia in the formalin test, or in the hotplate test. AP5 injections into the PAG reduced pain in the formalin test, but not the hotplate test. These data show that NMDA receptors within the PAG are involved in the perception of tonic, inescapable pain as measured in the formalin test, but not phasic, escapable pain as measured in the hotplate test.