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R Melzack

Publications and source records attributed to R Melzack.

At least 37 records · Page 2Linked to original sources
PubMed1996

Delayed nociceptive response following cold-water swim in the formalin test: possible mechanisms of action.

Exposure of animals to aversive events produces stress-induced analgesia. A common method of producing stress in animals is the cold-water swim (CWS). The present series of experiments examines the effect of CWS on tonic pain, as measured by the formalin test, and explores possible mechanisms of action. Experiment 1 demonstrates that a 3.5-min swim in 2 degrees C water produces a delayed nociceptive response (DNR), characterized by a prolonged period of no formalin responding which then begins and continues during the time when control animals, which have not received the CWS, are finished responding. The delayed response begins at 50-60 min postformalin injection, peaks at 80 min, and is still present at 120 min. Experiment 2 indicates that paw temperature effects are not responsible for the DNR, although core body temperature effects are a possible mechanism. However, systematic delays in the formalin injection following the CWS (Experiment 3) drastically altered the DNR even though core body temperature remained unchanged, suggesting that a decrease of core body temperature is insufficient to account for the DNR. Experiment 4 demonstrates that the NMDA antagonist MK-801 administered prior to the CWS dramatically reduces the DNR. The present experiment is the first study that reports a delay as long as 60 min in pain responding. It is concluded that the delayed response to formalin injection is the result of complex interactions involving peripheral mechanisms and central neuronal plasticity in which activity initiated by a noxious input persists after the cessation of the input as a consequence of a stressful event such as the cold-water swim.

Animals↗
PubMed1996

Restraint reduces formalin-test pain but the effect is not influenced by lesions of the hypothalamic paraventricular nucleus.

Previous research indicates that the paraventricular nucleus of the hypothalamus (PVN) plays an important role in the development of stress-induced analgesia (SIA). Research implicating the PVN in SIA has generally employed the cold-water swim as the stressor and a phasic pain test, such as the tail-flick test, as the pain model. The present study, using the formalin test for tonic pain, investigated the effect of PVN lesions on (1) tonic pain responses and (2) SIA caused by 30 min of restraint. Male Long-Evans rats were randomly assigned to one of four groups. Two groups received electrolytic lesions of the PVN and two additional groups served as sham-operated controls. One group which received PVN lesions and one group which was sham-operated were exposed to 30 min of restraint immediately prior to a 0.05-ml injection of 2.5% formalin into the planter surface of one hindpaw. The remaining groups which either received PVN lesions or were sham-operated received the formalin injection without prior exposure to restraint. During the first phase of the formalin response, PVN lesions did not alter duration of paw elevation scores, but significantly increased duration of paw licking scores. A 30-min period of restraint had no effect on duration of paw elevation scores, but significantly decreased duration of paw licking scores. PVN lesions did not alter the significant decrease in paw licking scores as a result of restraint. During the second phase of the formalin response, PVN lesions did not alter either the duration of paw elevation scores or the duration of paw licking scores. A 30-min period of restraint significantly decreased duration of paw elevation scores, but had no effect on duration of paw licking scores. PVN lesions did not alter the significant decrease in paw elevation scores as a result of restraint. The results indicate that PVN lesions increase paw licking only during the first phase of the formalin response, with no other alterations in paw licking or duration of paw elevation. In addition, a 30-min period of restraint can produce short-term and long-term SIA for tonic pain. The short-term SIA is reflected as a decrease in paw licking, whereas the long-term SIA is reflected as a decrease in paw elevation. In addition, PVN lesions failed to alter SIA during both phases of the formalin test. The differential effect of restraint on pain responses during the two phases of the formalin test and the lack of effect of PVN lesions on SIA for tonic pain suggest that stress engages multiple endogenous pain inhibitory systems.

Analgesia↗
PubMed1996

The bee venom test: a new tonic-pain test.

The present study describes a new test of tonic pain to be used as an animal model of persistent pain. First, pain responses and edema produced by subcutaneous injection of increasing doses of honey bee venom into the hind paw of the rat were quantified. Second, the effect of morphine and aspirin on the pain responses was investigated. Finally, the response to concurrent injections of bee venom and formalin was examined. Subcutaneous injection of bee venom produced local inflammation, tonic-pain responses lasting from 10 min to more than 1 h, and marked edema lasting from 3 h to more than 48 h. Increasing doses of bee venom produced higher mean pain scores and increased durations of responding. The time course of the edema did not follow the time course of the pain responses. Analgesia was produced by morphine and aspirin, indicating that the bee venom test can be used to test analgesic drugs. Concurrent administration of bee venom and formalin produced pain responses similar to formalin alone, with a less profound interphase depression and a longer duration. The data suggest that the bee venom test is a valid animal model of experimental tonic pain.

Analgesics, Non-Narcotic↗
PubMed1996

Positive intrasurgical suggestion fails to affect postsurgical pain.

The present study explored the effect of positive intrasurgical suggestion during the anesthetic state on postsurgical pain. One-half of the patients who were undergoing elective cholecystectomy or hysterectomy received strong positive intrasurgical suggestion directed specifically towards reducing pain. The control patients received information about pain without suggestion content. There was no effect on postsurgical pain measured by the McGill Pain Questionnaire and a visual analogue scale. The lack of effect on postsurgical pain indicates that intrasurgical suggestion does not provide a therapeutic method to achieve pain control.

Adult↗
PubMed1996

Properties of complex hallucinations associated with deficits in vision.

Complex visual hallucinations are known to occur in individuals with impaired vision yet whose emotional and intellectual functions are within the normal range. These hallucinations, which were first reported by Charles Bonnet in 1760, have been described in many case studies, but have not been analyzed empirically to determine their major properties. In the present study, sixty complex hallucinators labeled as Charles Bonnet hallucinators were administered a questionnaire to determine the properties of their hallucinations. Combined use of multiple-correspondence analysis and hierarchical cluster analysis reveals a set of features that characterize the 'typical' Charles Bonnet hallucinatory experience: the hallucinators' experience occurs while they are alert and with the eyelids open; a sharply focused image appears suddenly, without any apparent trigger or voluntary control; the hallucination is present for seconds, does not move during this time, then suddenly vanishes. These features are discussed in terms of a 'dimension' of hallucinatory/perceptual experience, which ranges from discrete perceptual experiences to multiple, changing experiences. Possible mechanisms that underlie the Charles Bonnet hallucinations are discussed.

Blindness↗
PubMed1995

Analgesia induced by morphine microinjection into the lateral hypothalamus of the rat.

Earlier studies have demonstrated that electrical stimulation of the lateral hypothalamus (LH) produces analgesia in tests of brief, phasic pain and more prolonged tonic pain. The present experiment examined the effect of morphine microinjection into the LH on formalin-induced pain. The results show that a 10-micrograms morphine microinjection significantly decreases pain responses. Moreover, the decrease persists for the duration of the 25-min test period, which began 25 min after the formalin injection. These findings suggest that electrical stimulation of the LH engages an endogenous opiate system which is capable of producing prolonged analgesia.

Analgesia↗
PubMed1995

Hypophysectomy produces analgesia and paraventricular lesions have no effect on formalin-induced pain.

Chemical destruction of the pituitary gland has been shown to alleviate severe cancer pain in a substantial proportion of patients. The underlying mechanisms, however, remain controversial. The present study investigated the effects of hypophysectomy in the formalin test, which provides an animal model of tonic pain, and attempted to determine a possible neural mechanism to explain the effectiveness of the procedure. Hypophysectomized rats displayed significantly less pain behavior in the formalin test than control rats that underwent a sham hypophysectomy, implicating the pituitary gland in the modulation of tonic pain. Since the paraventricular nucleus of the hypothalamus (PVN) provides a major source of input to the pituitary gland, the effects of electrolytic lesions of the PVN on tonic pain were examined. The results failed to show a significant effect of PVN lesions on pain responses in the formalin test. The results suggest that the pituitary gland modulates tonic pain in the formalin test and that the test provides an animal model to study possible mechanisms which underlie the relief of severe cancer pain by hypophysectomy. However, since PVN lesions did not affect the response of rats in the formalin test, it is possible that the PVN is only one of multiple interacting neural and endocrine structures that influence the functions of the pituitary.

Analgesia↗
PubMed1994

Phantom limb experiences in congenital limb-deficient adults.

This case report describes phantom limbs in four adults with congenital limb deficiency. Case 1, with congenital absence of the left arm below the elbow, received a minor injury of the stump at age 16 and subsequently developed a full-length phantom arm, hand and fingers. Cases 2 and 3, at the ages of 26 and 30, underwent minor surgery of the lower limbs and subsequently developed vivid, full-length phantoms of their legs. Case 4, aged 31, was born with a shortened and deformed right leg, and underwent amputation of the foot and deformed part of the leg at age 3. Beginning at age 6, she developed a full-length phantom leg and foot that touched the floor, which persisted for more than 20 years. The descriptions by these four adults lend credibility to earlier reports of phantom limbs in congenital limb-deficient children. They also indicate that these phantoms may persist into adulthood.

Abnormalities, Drug-Induced↗
PubMed1993

The habenula and pain: repeated electrical stimulation produces prolonged analgesia but lesions have no effect on formalin pain or morphine analgesia.

Recent studies have found that electrical stimulation of the habenula or microinjection of morphine into it reduces pain in several pain tests. The present study explored additional properties of the habenula. Expt. 1 examined the influence of the duration of stimulation on the duration of poststimulation analgesia in the formalin test. Expt. 2 was carried out to determine whether destruction of the habenula would affect either baseline pain levels or analgesia produced by morphine administered systemically in the formalin test. The results showed that the duration of analgesia is related to the duration of electrical stimulation. However, habenular lesions did not affect baseline pain levels or morphine analgesia. These studies support earlier evidence that manipulation of the habenula can produce analgesia, but suggest that it is not tonically active in modulating pain or necessary for the analgesic effects of systemically administered morphine.

Animals↗
PubMed1993

Pain: past, present and future.

Descartes' concept that pain is produced by a direct, straight-through transmission system from injured tissues in the body to a pain centre in the brain has dominated pain research and therapy until recently. The gate control theory of pain, published in 1965, proposes that a mechanism in the dorsal horns of the spinal cord acts like a gate which inhibits or facilitates transmission from the body to the brain on the basis of the diameters of the active peripheral fibers as well as the dynamic action of brain processes. As a result, psychological variables such as past experience, attention and other cognitive activities have been integrated into current research and therapy on pain processes. The gate control theory, however, is not able to explain several chronic pain problems, such as phantom limb pain, which require a greater understanding of brain mechanisms. A new theory of brain function, together with recent research that has derived from it, are described. They throw light on complex pain problems and have important implications for basic assumptions in psychology.

Afferent Pathways↗
PubMed1993

Visual hallucinations and mental state. A study of 14 Charles Bonnet syndrome hallucinators.

Complex visual hallucinations are usually a sign of acute psychopathology or gross cognitive impairment, but may also occur in people with visual deficits--the Charles Bonnet Syndrome. The mental state of 14 Charles Bonnet hallucinators was assessed using four psychological tests: the Beck Depression Inventory, the State-Trait Anxiety Inventory, the Mini-Mult, and the Mini-Mental State Examination. Results are consistent with earlier reports suggesting that these hallucinations are not due to psychopathology or compromised cognitive functioning. It is proposed that these complex visual hallucinations represent ongoing neural activity in the visual system following eye damage.

Aged↗
PubMed1992

Amitriptyline produces analgesia in the formalin pain test.

A dose of 20 mg/kg of amitriptyline reduced pain in the second phase of the formalin test, which is an animal model of long-lasting pain in humans. Since the analgesic effect was produced by a single dose, which is insufficient to produce an antidepressant effect, these results indicate that amitriptyline has analgesic properties that are independent of its antidepressant properties.

Amitriptyline↗
PubMed1992

Analgesic and aversive effects of naloxone in BALB/c mice.

Opioid antagonists have been shown to produce dose-dependent analgesia in the formalin test in BALB/c mice. In light of this paradoxical finding, the motivational-affective property of naloxone was examined in BALB/c mice. Naloxone produced a conditioned place aversion at doses which were also found to produce analgesia in the formalin test (1 and 10 mg/kg). In addition, the analgesia produced by 1 mg/kg naloxone was completely abolished in mice pretreated with nor-binaltorphimine, a highly selective kappa-opioid antagonist. Norbinaltorphimine on its own, however, had no effect. These results suggest that the analgesic actions of naloxone may be due to an interaction with kappa receptors.

Analgesia↗
PubMed1992

Multiple phantom limbs in a child.

This case report describes multiple phantom feet in a child after amputation of a leg. The subject is a 16-year-old girl who was born with a right leg 10 cm shorter than the left and who at the age of 6 was amputated below the right knee so that she could wear a prosthesis that would give her normal mobility. The girl reports that she subsequently experienced 2 phantom feet and 3 sets of phantom toes which have persisted to the present time. Each phantom has a distinct size, length and position in relation to the others and each is also the site of vivid sensations such as heat, tickle, and fatigue as well as voluntary and involuntary movement. She also describes sensations that resemble sensations experienced before the amputation: one of her phantom feet feels flat and locked into a forward position which corresponds with the actual shape and position of her congenitally deformed amputated foot. The implications of multiple phantoms are discussed with reference to recent concepts of phantom limbs.

Adolescent↗
PubMed1992

Phantom limbs.

Explore the source record for details and available documents.

Amputation, Surgical↗
PubMed1992

The contribution of excitatory amino acids to central sensitization and persistent nociception after formalin-induced tissue injury.

The contribution of excitatory amino acids (EAAs) to the development of central sensitization and persistent nociception in response to tissue injury in rats was examined following the subcutaneous injection of formalin into the hindpaw. Formalin-induced nociceptive behaviors were enhanced by intrathecal pretreatment with the EAAs L-glutamate and L-aspartate. An enhancement of the formalin nociceptive response was also produced by intrathecal pretreatment with the receptor-selective EAA agonists NMDA and trans-(+/- )-1-amino-1,3-cyclopentane dicarboxylic acid (ACPD), but not (R,S)-alpha-amino-3-hydroxy-5-methylisozazole-4-propionic acid hydrobromide (AMPA). The effect of NMDA was enhanced by a combined administration with AMPA or APCD. Formalin nociceptive responses were dose-dependently reduced by intrathecal pretreatment with the NMDA receptor antagonists 2-amino-5-phosphonovaleric acid (APV) and (+)-MK-801 hydrogen maleate, but not the selective AMPA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione or the selective metabotropic EAA receptor antagonist 2-amino-3-phosphonopropionic acid. The results suggest that EAAs acting at the NMDA receptor contribute to central sensitization and persistent nociception following subcutaneous formalin injection.

Amino Acids↗
PubMed1992

The role of NMDA receptor-operated calcium channels in persistent nociception after formalin-induced tissue injury.

The contribution of intracellular calcium to central sensitization and persistent nociception in response to tissue injury in rats was examined following the subcutaneous injection of formalin into the hindpaw. Formalin injury-induced nociceptive behaviors were enhanced by intrathecal pretreatment with the calcium ionophore A23187 or the calcium channel agonist Bay-K8644. Conversely, formalin nociceptive responses were reduced by intrathecal pretreatment with the calcium chelator Quin 2 or the calcium channel antagonists verapamil and nifedipine. Each of these agents affected the tonic, but not the acute, phase of the formalin response. The enhancement in formalin nociceptive behavior in rats treated with L-aspartate or L-glutamate was reversed by combined pretreatment with the noncompetitive NMDA antagonist MK-801, but not by nifedipine or the non-NMDA excitatory amino acid antagonist 6-cyano-7-dinitroquinoxaline-2,3-dione. In rats not treated with excitatory amino acids, the analgesic effect of MK-801 was also significantly greater than that produced by nifedipine. Furthermore, combining nifedipine with MK-801 did not produce a significantly greater analgesic effect than MK-801 alone. The results suggest that central sensitization and persistent nociception following formalin-induced tissue injury are dependent on the influx of calcium through predominantly NMDA receptor-operated (and to a lesser extent voltage-gated) calcium channels.

Animals↗