Biomedical subjects
Publications and source records attributed to R Melzack.
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.
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.
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.
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.
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.
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The contribution of C-fiber neuropeptides and excitatory amino acids (EAAs) as central mediators of secondary hyperalgesia was assessed by examining the effects of intrathecal (i.t.) administration of receptor-selective agonists and antagonists on foot-withdrawal latencies (from 48 degrees C water), both before and after heat injury of the contralateral hindpaw. The hyperalgesia which develops in the hindpaw contralateral to a heat injury, could be reproduced in uninjured rats following i.t. injection of substance P, neurokinin A and N-methyl-D-aspartate (NMDA) but not following calcitonin gene related peptide (CGRP), neurokinin B, kainate or (R,S)-alpha-amino-3-hydroxy-5-methylisozazole-4-propionic acid hydrobromide (AMPA). Contralateral hyperalgesia was reversed by the substance P antagonist Arg1,D-Pro2,D-Phe2-D-His9-substance P, and the NMDA receptor antagonist D-2-amino-5-phosphonovalerate (APV), but not by the non-NMDA EAA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When the limb of the injured hindpaw was pretreated with the C-fiber neurotoxin capsaicin, hyperalgesia in the contralateral hindpaw was unaffected. Furthermore, prior to injury, the capsaicin pretreatment itself produced hyperalgesia in the contralateral hindpaw. The results give support for a contribution of both C-fiber neuropeptides and EAAs to central nervous system plasticity and secondary hyperalgesia following heat injury.
Peripheral neurectomy in rats is followed by self-mutilation of the denervated zone (autotomy), which is assumed to represent an index of pain or dysesthesia associated with deafferentation. This study examines the role of the cingulum bundle in mediating autotomy behavior. Rats were given bilateral injections of 1 microliter of 0.5% bupivicaine (a local anesthetic) or saline into the cingulum bundle immediately prior to, and on Days 1, 7, 14, and 21 after, sectioning the sciatic and saphenous nerves. Bupivicaine injections into the cingulum produced a significant delay in the onset of self-mutilation and reduced the overall degree of autotomy. Furthermore, the delayed onset of autotomy exceeded the duration of the anesthetic block produced by bupivicaine.
The purpose of this study was to determine whether women in labor report less pain when they are in a vertical (sitting or standing) position than in a horizontal (side-lying or supine) position. Pain scores were obtained from 60 women in early labor (dilation 2-5 cm) who alternated between the two positions. The results show that about 35% of women feel less front pain and 50% feel less back pain when they are in a vertical position than in a horizontal position. The decrease in continuous back pain (83%) was particularly impressive, but the front and back pains associated with contractions were significantly diminished as well. These results, taken together with those of earlier studies, indicate that many women in early labor have less pain and are generally more comfortable in a vertical than in a horizontal position. Since early labor comprises a substantial proportion of the entire process of labor and delivery, any simple procedure which alleviates pain without danger to mother or child, such as shifting from a horizontal to a vertical position, should be promoted and employed.
The present study was designed to examine the prevalence and characteristics of painful and paresthetic sensations in a group of patients with healed burns. Adult patients who had been hospitalized for burn injuries during a 7-yr period were contacted and given a structured interview that included a series of questions about their present condition. Patients' medical charts were reviewed to obtain relevant demographic and medical information. The results show that abnormal sensations in healed burns are frequently reported as long as several years after the injury. Of 104 patients interviewed 1 yr or more after a burn injury, 82% reported paresthetic sensations such as tingling, stiffness, cold sensations, and numbness; and 35% complained of pain in the scarred tissue. The prevalence of these sensations was not related to age, sex, or etiology of the burns, but was associated with burn size and skin grafting. The theoretical and clinical implications of these results are discussed with particular emphasis on the need to pursue research on the long-term adverse effects of burn injuries.
The present paper evaluates the efficacy of low frequency, high intensity auricular transcutaneous electrical nerve stimulation (TENS) for the relief of phantom limb pain. Auricular TENS was compared with a no-stimulation placebo condition using a controlled crossover design in a group of amputees with (1) phantom limb pain (Group PLP), (2) nonpainful phantom limb sensations (Group PLS), and (3) no phantom limb at all (Group No PL). Small, but significant, reductions in the intensity of nonpainful phantom limb sensations were found for Group PLS during the TENS but not the placebo condition. In addition, 10 min after receiving auricular TENS, Group PLP demonstrated a modest, yet statistically significant decrease in pain as measured by the McGill Pain Questionnaire. Ratings of mood, sleepiness, and anxiety remained virtually unchanged across test occasions and sessions, indicating that the decrease in pain was not mediated by emotional factors. Further placebo-controlled trials of auricular TENS in patients with phantom limb pain are recommended in order to evaluate the importance of electrical stimulation parameters such as pulse width and rate, and to establish the duration of pain relief.
The Charles Bonnet syndrome is a condition in which individuals experience complex visual hallucinations without demonstrable psychopathology or disturbance of normal consciousness. An analysis of the sixty-four cases described in the literature reveals that the syndrome can occur at any age though it is more common in elderly people. Reduction in vision, due to peripheral eye pathology as well as pathology within the brain, is associated with the syndrome. Individual hallucinatory episodes can last from a few seconds to most of the day. Episodes can occur for periods of time ranging from days to years, with the hallucinations changing both in frequency and in complexity during this time. The hallucinations may be triggered or stopped by a number of factors which may exert their effect through a general arousal mechanism. People, animals, buildings, and scenery are reported most often. These images may appear static, moving in the visual field, or animated. Emotional reaction to the hallucinations may be positive or negative. Several theories have been proposed to account for the hallucinations. This paper highlights the sensory deprivation framework, with particular emphasis on the activity in the visual system after sensory loss that produces patterns of nerve impulses that, in turn, give rise to visual experience.
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)
Traditional neurosurgical methods to control pain have been replaced by a variety of modulation techniques. The major types of modulation are pharmacological, physical, and psychological. Important advances are occurring in the development of all three modulation approaches.
Evidence is presented which suggests that central neural changes occur during the brief early phase after subcutaneous formalin injection that are essential for the expression of pain during the long-lasting (tonic) later phase. First, tonic pain responses to subcutaneous formalin injections are abolished only if the injected hindpaw is locally anesthetized at the time of injection as well as the time of testing (30-60 min later). Second, tonic formalin pain is substantially reduced by brief spinal anesthesia given 5 min before, but not 5 min after the formalin injection.
The phenomenon of a phantom limb is a common experience after a limb has been amputated or its sensory roots have been destroyed. A complete break of the spinal cord also often leads to a phantom body below the level of the break. Furthermore, a phantom of the breast, the penis, or of other innervated body parts is reported after surgical removal of the structure. A substantial number of children who are born without a limb feel a phantom of the missing part, suggesting that the neural network, or 'neuromatrix', that subserves body sensation has a genetically determined substrate that is modified by sensory experience.
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