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J N Campbell

Publications and source records attributed to J N Campbell.

At least 19 recordsLinked to original sources
PubMed1999

Uninjured C-fiber nociceptors develop spontaneous activity and alpha-adrenergic sensitivity following L6 spinal nerve ligation in monkey.

We investigated whether uninjured cutaneous C-fiber nociceptors in primates develop abnormal responses after partial denervation of the skin. Partial denervation was induced by tightly ligating spinal nerve L6 that innervates the dorsum of the foot. Using an in vitro skin-nerve preparation, we recorded from uninjured single afferent nerve fibers in the superficial peroneal nerve. Recordings were made from 32 C-fiber nociceptors 2-3 wk after ligation and from 29 C-fiber nociceptors in control animals. Phenylephrine, a selective alpha1-adrenergic agonist, and UK14304 (UK), a selective alpha2-adrenergic agonist, were applied to the receptive field for 5 min in increasing concentrations from 0.1 to 100 microM. Nociceptors from in vitro control experiments were not significantly different from nociceptors recorded by us previously in in vivo experiments. In comparison to in vitro control animals, the afferents found in lesioned animals had 1) a significantly higher incidence of spontaneous activity, 2) a significantly higher incidence of response to phenylephrine, and 3) a higher incidence of response to UK. In lesioned animals, the peak response to phenylephrine was significantly greater than to UK, and the mechanical threshold of phenylephrine-sensitive afferents was significantly lower than for phenylephrine-insensitive afferents. Staining with protein gene product 9.5 revealed an approximately 55% reduction in the number of unmyelinated terminals in the epidermis of the lesioned limb compared with the contralateral limb. Thus uninjured cutaneous C-fiber nociceptors that innervate skin partially denervated by ligation of a spinal nerve acquire two abnormal properties: spontaneous activity and alpha-adrenergic sensitivity. These abnormalities in nociceptor function may contribute to neuropathic pain.

Adrenergic alpha-Agonists↗
PubMed1999

Electrophysiological assessment of the cutaneous arborization of Adelta-fiber nociceptors.

Little is known about the relationship between the branching structure and function of physiologically identified cutaneous nociceptor terminals. The axonal arborization itself, however, has an impact on the afferent signal that is conveyed along the parent axon to the CNS. We therefore developed electrophysiological techniques to investigate the branching structure of cutaneous nociceptors. Single-fiber recordings were obtained from physiologically identified nociceptors that innervated the hairy skin of the monkey. Electrodes for transcutaneous stimulation were fixed at two separate locations inside the receptive field. For 32 Adelta-fiber nociceptors, distinct steps in latency of the recorded action potential were observed as the intensity of the transcutaneous electrical stimulus increased, indicating discrete sites for action potential initiation. The number of discrete latencies at each stimulation location ranged from 1 to 9 (3.7 +/- 0. 2; mean +/- SE) and the mean size of the latency step was 9.9 +/- 1. 0 ms (range: 0.4-89.1 ms). For seven Adelta fibers, collision techniques were used to locate the position of the branch point where the daughter fibers that innervated the two locations within the receptive field join the parent axon. To correct for changes in electrical excitability at the peripheral terminals, collision experiments between the two skin locations and between each skin location and a nerve trunk electrode were necessary. Nine branch points were studied in the seven Adelta fibers; the mean propagation time from the action potential initiation site to the branch point was 31 +/- 5 ms corresponding to a distance of 54 +/- 10 mm. Almost half of the daughter branches were unmyelinated. These results demonstrate that collision techniques can be used to study the functional anatomy of physiologically identified nociceptive afferent terminals. Furthermore these results indicate that some nociceptive afferents branch quite proximal to their peripheral receptive field. Occlusion of action potential activity can occur in these long branches such that the shorter branches dominate in the response to natural stimuli.

Action Potentials↗
PubMed1998

Neuropathic pain following partial nerve injury in rats is suppressed by dietary soy.

Some humans with partial nerve injury present a syndrome of neuropathic sensory disorders which depend on the sympathetic activity (sympathetically-maintained pain, SMP). Several years ago we introduced a rat model for SMP, produced by tightly ligating 1/3-1/2 of the sciatic nerve, leading to a partial denervation of the hindpaw (Partial Sciatic Ligation, PSL model) [Seltzer, Z., Dubner, R. and Shir, Y., Pain, 43 (1990) 245-250]. After working with this model for several years we encountered difficulties in replicating it although rat strain, vendor, gender, age and weight, surgical approach and sensory testing procedures were not changed. We report here that this variability can be attributed, at least in part, to the diet the animals consumed. Rats fed perioperatively with soy-containing diets expressed significantly weaker neuropathic sensory disorders compared to rats fed on soy-free diets. We conclude that diet may greatly affect experimental outcome in the PSL model.

Animals↗
PubMed1998

Treatment of intractable pain with topical large-dose capsaicin: preliminary report.

UNLABELLED: Complex regional pain syndromes (CRPS) and neuropathic pain are often poorly controlled by conventional pharmacologic interventions. We administered 8-methyl-N-vanillyl-noneamide (capsaicin) at doses of 5%-10% to individuals with such disorders in this trial. Previous limitations to trials with larger-dose, topical concentrations of capsaicin included intense burning sensations experienced after application. To enable patients to tolerate the high concentrations, we first performed regional anesthesia. All patients reported at least some relief. Of 10 patients, 9 obtained substantial analgesia that lasted 1-18 wk. At Week 1 after therapy, the mean verbal analog scale (VAS) scores decreased from 8.0 to 3.0. At Week 4 after therapy, mean VAS score was 4.5. Analgesia lasted from < 1 wk (1 patient) to more than 50 wk (1 patient). Patients received one to eight treatments. With one exception, patients receiving more than one treatment obtained additional relief with subsequent treatment. Pain responsive to opioids was the only side effect of treatment. Large-dose capsaicin administered with regional anesthesia may effectively minimize refractory CRPS and neuropathic pain. A double-blind, placebo-controlled study in patients with bilateral peripheral neuropathy using epidural anesthesia with and without large-dose topical capsaicin is in progress. IMPLICATIONS: Sensory neuropathies are associated with many diseases. Pain from these disorders can produce greater disability than the primary disease processes themselves. Currently available therapies are limited. However, the intermittent application of large-dose topical capsaicin may provide significant pain relief, decrease chronic analgesic dependence, and decrease aggregate health care expenditures.

Administration, Topical↗
PubMed1998

Myelinated mechanically insensitive afferents from monkey hairy skin: heat-response properties.

To compare the heat responses of mechanically sensitive and mechanically insensitive A-fiber nociceptors, an electrical search technique was used to locate the receptive fields of 156 A-fibers that innervated the hairy skin in the anesthetized monkey (77 A beta-fibers, 79 A delta-fibers). Two-thirds of these afferents were either low-threshold mechanoreceptors (n = 91) or low-threshold cold receptors (n = 11). Nine A beta-fibers and 41 A delta-fibers were cutaneous nociceptors, and four A delta-fibers innervated subcutaneous tissue. The majority of cutaneous A-fiber nociceptors were heat sensitive (43/50 = 86%). Heat-insensitive cutaneous A-fiber nociceptors consisted of one cold nociceptor, three silent nociceptors, and three high-threshold mechanoreceptors. Two types of response were observed to an intense heat stimulus (53 degrees C, 30 s). Type I (n = 26) was characterized by a long latency (mean: 5 s) and a late peak discharge (16 s). Type II (n = 17) was characterized by a short latency (0.2 s) and an early peak discharge (0.5 s). Type I fibers exhibited faster conduction velocities (25 vs. 14 m/s) and higher heat thresholds (> 53 vs. 47 degrees C, 1-s duration) than type II fibers. The possibility that the type I heat response was a result of sensitization was tested in three fibers by determining the heat threshold to 30-s duration stimuli (42-46 degrees C). For this long stimulus duration heat thresholds were reproducible across multiple runs, and the threshold to the 1-s duration stimulus was not altered by these tests. Thus fibers with a type I heat response were not high-threshold mechanoreceptors that developed a heat response through sensitization. Fibers with a type II heat response had significantly higher mechanical thresholds (median: 15 bar) than fibers with a type I heat response (5 bar). This finding accounts for the observation that type II heat responses were infrequently observed in earlier studies wherein the search technique depended on mechanical responsiveness. Fibers with a type II response exhibited a graded response to heat stimuli, marked fatigue to repeated applications of heat stimuli, and adaptation to sustained heat stimuli similar to that seen in C-fiber nociceptors. First pain sensation to heat is served by type II A-fiber nociceptors that are mechanically insensitive. Type I A-fiber nociceptors likely signal pain to long-duration heat stimuli and may signal first pain sensation to mechanical stimuli.

Action Potentials↗
PubMed1998

Evidence for end-to-side sensory nerve regeneration in a human. Case report.

Division of a peripheral nerve produces an axotomy leading to neurite outgrowth from the proximal stump and wallerian degeneration in the distal stump. Because there is no longer a connection between the distal stump and neuronal cell bodies in the anterior spinal cord or dorsal root ganglion, it is assumed that no neurites should exist in the distal stump. The authors present the case of a patient who unexpectedly had a neuroma on the proximal end of the distal segment of a previously severed nerve. The lateral antebrachial cutaneous nerve had been surgically severed. Innervated by the radial nerve, a neuroma subsequently formed in the distal segment. Our hypothesis is that the proximal end of the distal portion of a severed nerve may be innervated by collateral sprouts of axons that branch at points of more distal plexus formation. This invokes a similar pathophysiology to the controversial notion of end-to-side nerve sprouting. Neuromas that develop on the "wrong side" of a nerve become an additional potential source of pain in patients with injured nerves.

Forearm↗
PubMed1996

Secondary hyperalgesia to mechanical but not heat stimuli following a capsaicin injection in hairy skin.

A psychophysical investigation was carried out to examine whether heat hyperalgesia exists within the secondary mechanical hyperalgesia zone surrounding a capsaicin injection site on hairy skin. A non-contact laser stimulator was used to deliver temperature controlled stimuli to sites within and outside the zone of mechanical hyperalgesia. Heat testing was carried out before and after the intradermal injection of 50 micrograms of capsaicin into the volar forearm. The zones of mechanical hyperalgesia to punctate and stroking stimuli and the region of flare were also mapped after the capsaicin injection. Heat pain thresholds inside the secondary mechanical hyperalgesic zone were not significantly different from thresholds outside the secondary mechanical hyperalgesia zone. In addition, pain ratings to an ascending series of heat stimuli delivered inside the zone of secondary hyperalgesia were not significantly different from pain ratings outside the zone of secondary hyperalgesia. Thus, there was no evidence for heat hyperalgesia within the zone of secondary hyperalgesia to punctate mechanical stimuli. Though the areas of punctate and stroking hyperalgesia were correlated, no correlation existed between the magnitude of capsaicin evoked pain and the areas mechanical hyperalgesia to punctuate and stroking stimuli or the area of flare. This suggests that independent mechanisms may mediate evoked pain, central sensitization that leads to mechanical hyperalgesia, and axon reflexive flare.

Analysis of Variance↗
PubMed1995

Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: estimates of receptor depth and threshold.

1. Responses to ramped or stepped temperature stimuli were obtained from fifty-three cutaneous C fibre mechano-heat nociceptors (CMHs) in the hairy skin of the pentobarbitone-morphine anaesthetized monkey. A three-layer heat transfer model was developed to describe the temperature distribution within the skin and to estimate receptor depth and heat threshold. 2. Surface heat threshold, defined as the surface temperature when the first action potential occurs, increased as: (a) the rate of temperature rise for the ramped stimuli increased from 0.095 to 5.8 degrees C s-1; (b) the duration of stepped heat stimuli decreased from 30 to 1 s; and (c) the base temperature of stepped heat stimuli decreased from 38 to 35 degrees C. These results suggest that the heat threshold for CMHs is determined by the temperature at the depth of the receptor. 3. Receptor depth estimates from responses to ramped stimuli ranged from 20 to 570 microns with a mean of 201 microns. The estimated mean receptor heat threshold was 40.4 +/- 2.2 degrees C (+/- S.D.). No correlation was observed between depth and thermal or mechanical threshold. The average receptor depth and threshold, estimated from the responses to stepped heat stimuli, were 150 microns and 40.2 degrees C, respectively. 4. We conclude that: (a) the receptor endings of CMHs occur in the epidermis and dermis; (b) temperature at the level of the receptor determines threshold; (c) temperature at the receptor ending is much lower than skin surface temperature at threshold; and (d) the tight distribution of receptor heat thresholds suggests a uniform transducer mechanism for heat in CMHs.

Animals↗
PubMed1995

Response of C fibre nociceptors in the anaesthetized monkey to heat stimuli: correlation with pain threshold in humans.

1. Ramped heat stimuli were used to compare the effects of rate of temperature change on the responses of monkey nociceptors and on heat pain threshold in human subjects. Recordings were made from twenty-five cutaneous C fibre mechano-heat nociceptors (CMHs) innervating the hairy skin in the anaesthetized monkey. Heat pain thresholds were determined on the volar forearm of eight human subjects using a converging staircase technique. 2. The heat pain threshold decreased as stimulus ramp rate increased. In contrast, the CMH heat threshold, defined as the surface temperature at which the first action potential occurred, increased as stimulus ramp rate increased. Thus, the properties of the heat stimulus that dictate heat pain threshold are different from the properties of the heat stimulus that govern the initiation of a response in nociceptors. 3. Peak discharge frequency of CMHs during the heat ramp increased with stimulus ramp rate. Heat pain threshold was correlated with achievement of a minimum discharge rate in nociceptors (0.5 Hz), rather than with the threshold for action potential initiation.

Action Potentials↗
PubMed1995

Evidence for two different heat transduction mechanisms in nociceptive primary afferents innervating monkey skin.

1. Mechano- and heat-sensitive A fibre nociceptors (AMHs) and C fibre nociceptors (CMHs) in hairy skin (forty-six AMHs and twenty-one CMHs) and in glabrous skin (fifty-nine AMHs and ten CMHs) of anaesthetized monkeys were tested with a 30 s, 53 degrees C heat stimulus, delivered by a laser thermal stimulator (0.1 s rise time, 7.5 mm diameter). 2. Two types of heat response were observed in hairy skin AMHs. Type I AMHs had a peak discharge towards the end of the stimulus, response latencies to heat of up to several seconds, a median heat threshold greater than 53 degrees C, and a mean conduction velocity of 25 m s-1 (n = 33). Type II AMHs had a peak discharge within 1-3 s, a mean response latency of 120 ms, a median heat threshold of 46 degrees C, and a mean conduction velocity of 15 m s-1 (n = 13). Type I AMH fibres were sensitized to heat, whereas heat responses of type II AMHs were suppressed following the intense heat stimulus. 3. In glabrous skin, only type I AMHs were found. The absence of type II AMHs is consistent with the absence of first pain to heat in glabrous skin. 4. C fibre nociceptors in hairy skin had a peak discharge near stimulus onset, a mean response latency of 100 ms and a median heat threshold of 41 degrees C. Heat responses of CMHs in glabrous skin were not significantly different from those in hairy skin. 5. Only type II AMHs had response latencies that were short enough to explain first pain to heat. Heat thresholds of type II AMHs were significantly higher than those of CMHs. 6. These results suggest two different heat transduction mechanisms in nociceptive afferents. For one, heat energy is quickly transduced into action potentials, and the peak discharge is reached soon after stimulus onset. For the other, the transduction of heat is distinctly slower, and the peak discharge occurs near the end of the stimulus. Chemically mediated sensitization may be involved in the second transduction mechanism.

Animals↗
PubMed1995

An electromechanical stimulator system for neurophysiological and psychophysical studies of pain.

We have developed a computer-based electromechanical stimulator system suited for neurophysiological and psychophysical studies of pain. The core of the stimulator is a servo-controlled linear motor capable of generating 1 kg of force over a 22-mm range. Forces collinear and tangenital to the interchangeable probe tip are calculated using the signal from 3 load cells (resolution: 1/8 g; range: 250 g) arranged in an equilateral triangle. Probe position is measured with an optical encoder (resolution: 1 micron; range: 25 mm). A microprocessor-based digital control system permits smooth switching of feedback control between force or position at the 1-kHz update rate. The stimulator is mounted on a microprocessor-controlled 3-axis translation system that allows automatic movement of the probe over a range of greater than 15 cm to an accuracy of better than 10 microns. The stimulator can be programmed to move in a coordinate system parallel to the skin surface being examined. An IBM-compatible computer is used to command stimulus paradigms and to display real-time motor performance and neural spike-train data. The system has been used to measure the response of nociceptive afferents in monkey to controlled force stimuli applied to various positions within the receptive field.

Animals↗
PubMed1995

Nerve injury associated with laparoscopic inguinal herniorrhaphy.

BACKGROUND: As laparoscopic herniorrhaphy becomes more popular, it is important to realize the potential for injury to surrounding neural structures, with attendant severe disability. METHODS: Herein are discussed two patients with disabling neuralgia after laparoscopic herniorrhaphy. RESULTS: Both patients were treated with transabdominal removal of their prosthetic materials and anchoring staples, with dramatic symptomatic improvement. CONCLUSIONS: The surgeon should be aware of the anatomic considerations accompanying laparoscopic herniorrhaphy. In regard to nerve injury, laparoscopic herniorrhaphy may pose certain disadvantages over traditional hernia repairs. It may diminish the ability to appreciate the course of nerves in the inguinal region and their relationship to the spermatic cord, and injury to nerves may be difficult to recognize and treat.

Adult↗
PubMed1994

Cellular components necessary for mechanoelectrical transduction are conveyed to primary afferent terminals by fast axonal transport.

Axonal transport of neurotransmitter receptors is a well established phenomenon. In this study, we sought to determine whether the cellular components necessary for mechanical-to-electrical transduction in primary afferents are also conveyed to the peripheral terminals via fast axonal transport. In previous studies, severed cutaneous nerves have been shown to develop mechanical sensitivity at their ligated ends within hours of injury. Since the rate of development of this mechanical sensitivity was temperature dependent, we postulated that axonal transport was involved. In this study, we performed two experiments in which the rate of axonal transport was modified. In the first experiment, the nerve was cut at a proximal site to block the supply of additional transported components to the distal end of the nerve. At a point 80 to 120 mm distal to this proximal cut, a nerve crush and ligation were performed either 3 or 12 h after the proximal nerve ligation. The centripetally conducted action potentials generated by applying mechanical stimuli to the nerve subjacent to the distal ligature were recorded 10 h after the distal ligature was placed. Given a fast axonal transport rate of 400 mm/day, transported molecules should traverse a 100-mm segment within 6 h. Consistent with this calculation, 29% of the myelinated fibers responded to mechanical stimuli when the time lapse between lesions was 3 h, whereas only 3% responded when the time between lesions was 12 h. In the second experiment, axonal transport was enhanced by a prior nerve injury (conditioning lesion).(ABSTRACT TRUNCATED AT 250 WORDS)

Afferent Pathways↗
PubMed1994

Chronic opioid therapy as alternative treatment for post-herpetic neuralgia.

Neurosurgical procedures such as the dorsal root entry zone operation, ganglionectomy, and spinal-cord stimulation have been offered to patients with intractable post-herpetic neuralgia (PHN). Poor efficacy or high morbidity have limited the overall usefulness of these procedures. We recently conducted a preliminary open-label study with long-acting oral opioids. The mean pretreatment pain score, on a scale of 0 to 10 (0 = no pain) was 9.0 +/- 0.3 (mean +/- SEM, N = 20). At two months of treatment the average pain score was 4.0 +/- 0.4 (p < 0.001, paired t test), and at six months the average pain score was 3.8 +/- 0.2 (p < 0.001, N = 16). These observations warrant a controlled opioid trial for patients affected by PHN.

Adult↗
PubMed1994

A psychophysical study of secondary hyperalgesia: evidence for increased pain to input from nociceptors.

Substantial evidence suggests that the hyperalgesia to mechanical stimuli that occurs in an area of uninjured skin surrounding a site of injury (area of secondary hyperalgesia) arises from activity in low-threshold mechanoreceptors (LTMs). In this study, we have investigated if activity in mechanically sensitive nociceptors also contributes to this secondary hyperalgesia. It is known that all woollen fabrics excite LTMs, but that only the prickly ones activate mechanically sensitive nociceptors. Therefore, we have conducted a psychophysical study using a range of prickly and non-prickly woollen fabrics applied to normal and hyperalgesic skin to assess the roles of LTMs and nociceptors in secondary hyperalgesia. We have studied in 10 normal volunteers the sensations of fabric-evoked prickle and pain in normal and hyperalgesic skin. Secondary hyperalgesia was produced by intradermal injection of capsaicin (25 micrograms) into the volar skin of the forearm. Five woollen fabrics (2 non-prickly, 2 prickly and 1 intermediate) were presented, in a blind manner, to the skin before and after the capsaicin injection. The sensation of fabric-evoked prickle was not changed in hyperalgesic skin. On the other hand, little if any pain was evoked by the fabrics when applied to normal skin, but substantial pain was produced by all fabrics when applied to hyperalgesic skin. The pain ratings were graded with the ratings of prickle so that fabrics that evoked the greatest prickle also evoked significantly more pain. The magnitude of pain increased linearly with prickle sensation; the slope of this regression function increased substantially in hyperalgesic skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Chemosensitivity and sensitization of nociceptive afferents that innervate the hairy skin of monkey.

1. A large proportion of the cutaneous nociceptor population in monkey either does not respond to mechanical stimuli or has very high mechanical thresholds (> 6 bar). The goal of this study was to determine whether these mechanically insensitive nociceptive afferents (MIAs) differ from mechanically sensitive nociceptive afferents (MSAs) with regard to responses to chemical stimuli. 2. Teased-fiber techniques were used to record from 28 A delta-fiber (16 MIAs and 12 MSAs) and 23 C-fiber (10 MIAs and 13 MSAs) nociceptors in hairy skin of pentobarbital sodium-anesthetized monkeys. An electrocutaneous search technique was used to locate the putative receptive fields of the MIAs. The response to mechanical and heat stimuli was determined before and after intradermal injection of a standard mixture of algesic/inflammatory mediators (bradykinin, histamine, serotonin, and prostaglandin E1). 3. All 25 MSAs, but only 65% of the MIAs, responded to the chemical stimulus. The A delta-fibers, both MSAs and responsive MIAs, and the responsive C-fiber MIAs gave a robust discharge. In contrast, the C-fiber MSAs (the conventional polymodal C-fiber nociceptors) exhibited a significantly weaker response. Three MIAs responded only to the chemical mixture and not to mechanical or heat stimuli. 4. Before injection of the chemical mixture, a significantly smaller proportion of C-fiber MIAs (50%) than of C-fiber MSAs (92%) responded to heat stimuli, whereas a similar proportion (38%) of A delta-fiber MIAs and MSAs were heat sensitive. 5. Approximately one-half of the MIAs and MSAs were sensitized to mechanical stimuli after the chemical injection, as manifest by a decreased threshold and/or an enlarged receptive field. 6. The chemical injection sensitized 90% of A delta-fiber MSAs, but only 8% of A delta-fiber MIAs, to heat stimuli. In contrast, 38% of C-fibers were sensitized. 7. In 14 fibers, the chemical stimulus resulted in sensitization to mechanical stimuli without sensitization to heat stimuli, or vice versa. This dissociated sensitized state suggests that the molecular mechanisms of sensitization to heat and mechanical stimuli differ. 8. In conclusion, a large proportion of primate cutaneous nociceptors respond to intradermal injection of algesic/inflammatory mediators and may also become sensitized to mechanical and/or heat stimuli.

Animals↗