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Biomedical subjects

Richard A Meyer

Publications and source records attributed to Richard A Meyer.

12 recordsLinked to original sources
PubMed2002

Neuropathic pain after C7 spinal nerve transection in man.

Various animal models of neuropathic pain have been developed which involve creating a lesion in a spinal root. We describe a human correlate in which patients developed a neuropathic pain syndrome after having one spinal nerve surgically divided. In some patients with brachial plexus lesions, the C7 spinal nerve from the opposite side is divided and used as a nerve transfer to re-innervate the injured brachial plexus. Of five patients that underwent this procedure, one went on to develop a transient but significant neuropathic pain problem. Extensive sensory testing in this patient 2 months after surgery revealed dysesthesia and hyperalgesia to mechanical and cooling stimuli, but not to heat stimuli in the C7 dermatome of the hand on the side of C7 section. The pain and hyperalgesia persisted during a phentolamine infusion, which produced a sympathetic blockade. Only mild parasthesia persisted at a 1 year follow up. Thus, surgical division of a single spinal nerve in humans can lead to the development of neuropathic pain.

Adrenergic alpha-Antagonists↗
PubMed2002

Mechanical hyperalgesia after an L5 ventral rhizotomy or an L5 ganglionectomy in the rat.

An L5 spinal nerve ligation (SNL) in the rat leads to behavioral signs of mechanical hyperalgesia. Our recent finding that an L5 dorsal root rhizotomy did not alter the mechanical hyperalgesia following an L5 SNL suggests that signals originating from the proximal stump of the injured nerve are not essential. We postulate that Wallerian degeneration of L5 nerve fibers leads to altered properties of adjacent intact nociceptive afferents. To investigate the role of degeneration in sensory versus motor fibers, five injury models were examined concurrently in a blinded fashion. An L5 ganglionectomy produced a selective lesion of sensory fibers. An L5 ventral root rhizotomy produced a selective lesion of motor fibers. The three control lesions included: (1) SNL with L5 dorsal root rhizotomy; (2) L5 dorsal root rhizotomy; and (3) exposure of the L5 roots without transection (sham). Paw withdrawal thresholds to mechanical stimuli were measured at three sites in the rat hindpaw corresponding to the L3, L4, and L5 dermatomes. Both the ganglionectomy and the ventral rhizotomy produced a significant, lasting (>or=20 d) decrease of mechanical withdrawal thresholds that was comparable to that produced by the SNL lesion. The L5 dorsal rhizotomy, by itself, produced a short lasting (<or=6 d) decrease in thresholds, whereas the sham procedure did not produce a significant change. We propose that interactions between degenerating motor and sensory fibers of the injured nerve and intact afferent fibers of neighboring nerves play a critical role for both initiation and maintenance of mechanical hyperalgesia in neuropathic pain.

Animals↗
PubMed2000

Mechanical hyperalgesia after an L5 spinal nerve lesion in the rat is not dependent on input from injured nerve fibers.

An injury to a peripheral nerve in animals often leads to signs of neuropathic pain including hyperalgesia to heat, cold and mechanical stimuli. The role of injured and intact nerve fibers in mechanical hyperalgesia was evaluated in rats subjected to an L5 spinal nerve ligation-and-cut ('modified SNL lesion'). To assess the contribution of injured afferents, an L5 dorsal rhizotomy was performed immediately before, or 7 days after the modified SNL lesion. To study the role of adjacent intact spinal nerves, an L4 dorsal rhizotomy was performed 7 days after the modified SNL lesion. The up-down method of Dixon (Dixon WJ, Annu Rev Pharmacol Toxicol 1980;20:441-462) was used to measure the paw withdrawal threshold to mechanical stimuli at three sites on the rat hindpaw corresponding to the L3, L4, and L5 dermatomes. We found that the modified SNL lesion produced a significant, lasting (20 days) decrease of the mechanical withdrawal threshold. The severity and duration of mechanical hyperalgesia varied across testing sites. The L5 and L4 dermatome test sites developed the most severe and lasting mechanical hyperalgesia. In contrast, the L3 testing site developed significantly less severe and shorter lasting mechanical hyperalgesia. L5 dorsal rhizotomy, by itself, produced a transient decrease in mechanical withdrawal thresholds. L5 dorsal rhizotomy performed before, or 7 days after, the modified SNL lesion did not prevent or resolve the observed decrease in mechanical withdrawal thresholds. L4 dorsal rhizotomy performed 7 days after the modified SNL lesion resulted in an immediate reversal of mechanical withdrawal thresholds back to baseline values. These results suggest that, after L5 spinal nerve ligation-and-cut, mechanical hyperalgesia develops and persists independent of input from injured afferents. We propose that the Wallerian degeneration that develops after a nerve injury leads to interactions between the degenerating fibers of the injured spinal nerve and the intact fibers of adjacent spinal nerves. This leads to changes in the intact fibers that play a critical role for both initiation and maintenance of mechanical hyperalgesia.

Animals↗
PubMed2000

Intradermal injection of norepinephrine evokes pain in patients with sympathetically maintained pain.

Tissue injuries, with or without involvement of nerves, may lead to ongoing pain and hyperalgesia to external stimuli. In a subset of patients, the pain is maintained by sympathetic efferent activity (SMP). We investigated if the peripheral administration of the alpha-adrenergic agonist, norepinephrine (NE), in physiologically relevant doses resulted in pain in patients with SMP. To establish the dose of intradermal NE required to induce cutaneous vasoconstriction, NE (1 nM-10 microM, 30 microl) was injected under a laser Doppler probe on the volar forearm of seven normal subjects. A decrease in blood flow was evident at a dose of 10 microM. Twelve patients (five male, seven female) diagnosed to have SMP based on the decrease in pain by a local anesthetic sympathetic blockade (70+/-6%) were enrolled in the study. Pain ratings were obtained continuously for 5 min after intradermal injections of saline and NE (0.1-10 microM) into their hyperalgesic zone and the mirror-image contralateral side. Injections were done during the period of pain relief following a local anesthetic sympathetic blockade. Similar injections were made in eight control subjects. On the affected side of the patients, the two highest concentrations of NE (1 and 10 microM) caused significantly more pain than saline (P<0.05, ANOVA). In contrast, there was no significant pain induced by the NE injections in the unaffected side and in control subjects. Six of nine patients tested reported a marked decrease in pain and hyperalgesia following infusion of phentolamine (1 mg/kg over 10 min). Two of the three patients who did not receive pain relief following phentolamine infusion also did not report pain to the NE injections. We conclude that NE injections produce pain in SMP patients at doses that are at the threshold for producing vasoconstriction. These studies support a role for cutaneous adrenoceptors in the mechanisms of sympathetically maintained pain.

Adrenergic alpha-Agonists↗
PubMed1999

Topical EMLA pre-treatment fails to decrease the pain induced by 1% topical capsaicin.

Topical capsaicin has been reported to be beneficial for the treatment of neurogenic pain. However, due to the burning pain associated with topical capsaicin, many patients discontinue treatment before therapeutic benefits are obtained. This study assessed the efficacy of EMLA (eutectic mixture of 2.5% prilocaine and 2.5% lidocaine) to block pain induced by the topical application of 1% capsaicin. Nine healthy subjects (five males and four females) participated in the study. High dose topical capsaicin (1%) was applied to a 2.5 x 2.5 cm region of both volar forearms for 6 h. One arm was pretreated (for 2 h) and cotreated with EMLA, and the other arm served as vehicle control. Average and peak pain ratings were recorded at 15-min intervals using a 0 (no pain) to 10 (worst possible pain) scale. Average and peak pain ratings were significantly lower at the EMLA site during the first 15-30 min of capsaicin treatment. However, for the remaining 5.5 h of capsaicin treatment, the pain ratings at the EMLA and vehicle sites were not significantly different. The 6 h treatment with high dose topical capsaicin (1%) produced significant desensitization to heat stimuli that was not affected by EMLA treatment. EMLA fails to produce a long lasting attenuation of the pain induced by topical application of 1% capsaicin. These results argue against the use of EMLA to block pain to topical capsaicin during the treatment of neurogenic pain.

Administration, Topical↗
PubMed1999

C- and A delta-fiber components of heat-evoked cerebral potentials in healthy human subjects.

Feedback-controlled laser heat was used to stimulate the hairy skin of the hand dorsum and forearm, and heat-evoked cerebral potentials were recorded at midline (Fz, Cz, Pz) and temporal (T3, T4) scalp positions. Based on data from primary afferent electrophysiology a stimulus level (40 degrees C) was chosen, which is above C-fiber heat threshold, but clearly below A delta-nociceptor heat threshold in order to excite selectively C-fibers without concomitant excitation of A delta-fibers. Feedback-controlled stepped heat stimuli to 40 degrees C elicited ultralate laser evoked potentials (LEPs) at the vertex in a high proportion of experiments (90%). Estimates of conduction velocity calculated from latency shifts between the hand and forearm sites of ultralate LEPs (2.4 m/s) and of reaction times (2.8 m/s) confirmed mediation of ultralate potentials by unmyelinated nerve fibers (nociceptors and/or warm fibers). The ultralate LEP could be differentiated from resolution of contingent negative variation (CNV), an endogenous potential related to expectation and response preparation, by its scalp topography. Strong heat stimuli of 48 degrees C, which is suprathreshold for most A delta- and C-fiber nociceptors, elicited the well-known late LEPs mediated by nociceptive Adelta-fibers confirming previous studies. The LEP waveform to strong heat stimuli also contained an ultralate component reminiscent of an ultralate LEP following the late LEP. Ultralate and late LEP had identical scalp topography. In conclusion, the method of temperature-controlled laser heat stimuli allows the selective and reliable examination of A delta- and C-fiber-mediated afferent pathways and the related cortical processing without the complication of dissociating A-fiber nerve blocks.

Adult↗
PubMed1995

Cutaneous injection of the capsaicin analogue, NE-21610, produces analgesia to heat but not to mechanical stimuli in man.

Intradermal injection of the capsaicin analogue, NE-21610 (Procter and Gamble), inactivates nociceptors but not low-threshold mechanoreceptors in monkey. The present study examined the effects of cutaneous NE-21610 on heat and mechanical sensation in normal human volunteers. In the first series of experiments, subjects received intradermal (i.d.) injections (30 microliters) of the vehicle alone or with the drug (0.3, 3.0, 10 micrograms) into different sites on the volar forearm. Subjects were randomly assigned to 1 of 3 protocols to examine drug-evoked pain (n = 8), or alterations in pain to heat (n = 8) or mechanical (n = 8) stimuli induced by the drug. An additional 7 subjects rated pain to mechanical and heat stimuli before and after subcutaneous (s.c.) injections (300 microliters) of the vehicle or drug (100 micrograms). The peak pain occurred at the time of injection, was of short duration, and was similar for vehicle and drug injections. A mild, dose-related pain followed that lasted up to 2 h. Von Frey thresholds for detection, sharpness, and pain at the injection site (measured 24 h after injection) were not significantly altered by either i.d. or s.c. drug administration. However, pain to stepped heat stimuli was reduced in a dose-dependent fashion for both types of injection. At the highest drug doses, analgesia to heat stimuli was still present 1 week after injection. Recovery of heat sensitivity occurred several weeks after injection. This dissociated loss of heat but not mechanical pain sensibility may be due to: (1) a selective action of the drug on heat transducers in nociceptors responsive to both heat and mechanical stimuli, or (2) a selective action on that subset of nociceptors responsible for signaling heat-evoked pain.

Analgesia↗
PubMed1995

Cutaneous pretreatment with the capsaicin analog NE-21610 prevents the pain to a burn and subsequent hyperalgesia.

Cutaneous injection of the capsaicin analog NE-21610 (Procter and Gamble) produces analgesia to heat but not mechanical stimuli in humans. The present study examined whether pretreatment of the skin with NE-21610 prevents the development of hyperalgesia following heat injury. On the 1st day testing, 7 volunteers received a 30-microl intradermal injection of vehicle to one volar forearm and 10 micrograms of NE-21610 to the other volar forearm. On the 2nd test day the subjects rated the intensity of pain to mechanical and heat stimuli before and after a burn (48 degrees C, 120 sec) to each injection site. At the vehicle site, the pain evoked by the burn was rated as moderate to strong. In addition, primary hyperalgesia to heat and mechanical stimuli, secondary hyperalgesia to mechanical stimuli, and flare were observed after the burn. In contrast, the pain evoked by the burn at the NE-21610-treated site was rated as weak, and primary hyperalgesia to heat and mechanical stimuli did not develop. In addition, the area of flare at the drug-tested site was smaller than that observed at the vehicle site, and no secondary hyperalgesia to mechanical stimuli was observed. These data suggest that pretreatment with the capsaicin analog NE-21610 may attenuate the pain and hyperalgesia associated with injury.

Adult↗
PubMed1992

Sympathectomy does not abolish bradykinin-induced cutaneous hyperalgesia in man.

Bradykinin is an endogenous peptide that is thought to be a chemical mediator of the hyperalgesia following inflammation. In rat, bradykinin has been postulated to cause hyperalgesia to mechanical stimuli by releasing prostaglandin from sympathetic post-ganglionic terminals. The aim of this study was to determine whether bradykinin-induced cutaneous hyperalgesia in humans requires post-ganglionic sympathetic terminals. In humans, intradermal injection of bradykinin produces dramatic hyperalgesia to heat but not mechanical stimuli. Therefore, we measured the magnitude and duration of pain and hyperalgesia to heat stimuli following intradermal injection of bradykinin into the leg of a woman before and 6 months after an ipsilateral, surgical, lumbar sympathectomy. The pain and hyperalgesia to heat following bradykinin was found to be unaffected by the sympathectomy. These results suggest that the algesic effects of cutaneous bradykinin in human are independent of the sympathetic nervous system.

Adolescent↗
PubMed1988

Myelinated afferents signal the hyperalgesia associated with nerve injury.

Pain to light touching of the skin is a hallmark sign of causalgia. The purpose of this study was to determine whether myelinated or unmyelinated afferent fibers signal this hyperalgesia. Sensory testing was performed in 17 patients with long-standing hyperalgesia after nerve injury. The patients underwent a differential ischemic block of nerve function of the involved area. At a time when touch sensation in adjacent normal skin was eliminated, but when sensibility to warming and cooling stimuli was unaffected, the hyperalgesia to mechanical stimuli was abolished in 15 of the subjects. In 2 of these 15 patients, a differential local anesthetic block of the injured nerve was performed proximal to the site of injury. When temperature sensibility was absent, but when touch sensation was intact, hyperalgesia was present. In a third study, latency measurements in response to 400 micron stepped displacement stimuli were made in two patients who had hyperalgesia on the foot. The mean latency for detection of pain in the hyperalgesic region was 414 +/- 18 msec, compared to 458 +/- 16 msec for the detection of touch to the same stimuli applied to the opposite normal foot. These 3 lines of evidence indicate that myelinated primary afferents, perhaps A beta fibers, signal the hyperalgesic pain in causalgia. These fibers may be sensitized A beta nociceptors or low-threshold mechanoreceptors.

Adult↗
PubMed1988

Responses to heat of C-fiber nociceptors in monkey are altered by injury in the receptive field but not by adjacent injury.

We sought to determine the effects of a cut injury on the thermal responsiveness of C-fiber nociceptors sensitive to heat and mechanical stimuli (CMHs). Teased fiber techniques were used to record from single CMHs that innervated the hairy skin of the monkey arm. Responses to heat stimuli ranging from 41 to 49 degrees C were compared before and after injury. In 11 CMHs, the injury was applied 4 mm peripheral to the edge of the receptive field. The response to the heat sequence was not significantly altered by this adjacent injury. In 16 CMHs, a cut was applied directly to the receptive field. This direct injury led to a significant increase in response to the sequence of heat stimuli (i.e., sensitization). It is concluded that spreading sensitization of C-fiber nociceptors to a cut injury does not occur in monkey.

Animals↗