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At least 19 recordsLinked to original sources
PubMed1996

Clonidine, but not morphine, delays the development of thermal hyperesthesia induced by sciatic nerve constriction injury in the rat.

BACKGROUND: It has been shown that the spinal facilitation induced by the injury discharge evoked by a nerve constriction injury is crucial in the development of thermal hyperesthesia. Both opioids and alpha 2 agonists have been reported to prevent the development of spinal facilitation evoked by the small afferent input to the spinal cord. Moreover, it has been reported that the thermal hyperesthesia induced by a nerve constriction injury is sympathetically maintained and that spinally administered alpha 2 agonists can modulate the sympathetic outflow from the spinal cord. The current study investigated the effect of spinally administered morphine and clonidine, an alpha 2 agonist, on the development of thermal hyperesthesia induced by nerve constriction injury in the rat. METHODS: A model of thermal hyperesthesia induced by a constriction injury created by making four loose ligatures around the rat sciatic nerve was used to examine the development of thermal hyperesthesia. Morphine, clonidine, and idazoxan were administered intrathecally or intraperitoneally 20 min before (pretreatment study) or 20 min after (posttreatment study) the nerve injury. RESULTS: Pretreatment, but not posttreatment, with intrathecal clonidine significantly delayed the development of thermal hyperesthesia in a dose-dependent manner, and this delay in onset produced by clonidine was 3 days after the nerve injury. This effect of clonidine's was completely antagonized by the coadministration of idazoxan with clonidine. Intrathecal morphine had no effect on the development of thermal hyperesthesia in this study. CONCLUSIONS: Spinal alpha 2 receptors, but not opioid receptors, may play an important role in the development of thermal hyperesthesia induced by a nerve constriction injury. This suggested that the activation of spinal alpha 2 receptor may reduce the sympathetic outflow and this reduction of sympathetic outflow may be the key mechanism that delays the development of thermal hyperesthesia.

Adrenergic alpha-Agonists↗
PubMed1993

Effects of FK224, a novel cyclopeptide NK1 and NK2 antagonist, and CP-96,345, a nonpeptide NK1 antagonist, on development and maintenance of thermal hyperesthesia evoked by carrageenan injection in the rat paw.

BACKGROUND: The role of tachykinins, such as substance P and neurokinin A, in the development or maintenance of thermal hyperesthesia during inflammation is unclear. In the current study, the authors examined the role of NK1 and NK2 receptors on the thermal hyperesthesia evoked by injection of carrageenan into the rat paw using FK224, a cyclopeptide NK1 and NK2 antagonist, and CP-96,345, a nonpeptide NK1 antagonist. METHODS: In rats injected with 2 mg carrageenan, the paw withdrawal latency (PWL) for the injected paw was typically 5-6 s less than that for the untreated paw, at 2 h after the carrageenan injection. In the pretreatment study, drugs were administered intravenously or intrathecally 10 min before the carrageenan injection. In the posttreatment study, drugs were administered intravenously or intrathecally 2 h after the carrageenan injection. RESULTS: In the pretreatment study, both intravenous CP-96,345 and intravenous FK224 blocked the development of thermal hyperesthesia and reduced paw edema in a dose-dependent manner 2 h after the carrageenan injection. The effect of CP-96,345 on thermal hyperesthesia was stereospecific, but that on paw edema was not. Posttreatment with intravenous CP-96,345 and intravenous FK224 failed to reduce the level of thermal hyperesthesia or paw edema, and intrathecal injections, either pre- or posttreatment, had no effect on thermal hyperesthesia or paw edema. CONCLUSIONS: These data indicate that: 1) spinal NK1 and NK2 receptors do not play an important role in development and maintenance of thermal hyperesthesia evoked by paw carrageenan, and 2) the peripheral NK1 receptor may play an important role in the development of thermal hyperesthesia, but not of paw edema.

Animals↗
PubMed1995

OP-1206, a prostaglandin E1 derivative, attenuates the thermal hyperesthesia induced by constriction injury to the sciatic nerve in the rat.

Nerve ischemia induces wallerian degeneration and peripheral neuropathy, the nerve constriction injury induces thermal hyperesthesia. Nerve ischemia is one possible mechanism in the development of thermal hyperesthesia in the nerve constriction injury model. Prostaglandin E1 increases tissue blood flow. In the present study, the authors examine the role of nerve ischemia in the maintenance of the thermal hyperesthesia induced by nerve constriction injury by orally administering OP-1206, a prostaglandin E1 derivative. A nerve constriction injury model was created by making four loose ligations around the rat sciatic nerve, which induces thermal hyperesthesia in the ligated paw in 2-5 days. OP-1206, was administered six times (Day 7, one time; Day 8, two times; Day 9, two times; Day 10, one time). A single administration of OP-1206 had no effect on the thermal hyperesthesia. Six hours after the sixth-administration of OP-1206, the level of the thermal hyperesthesia was attenuated in a dose-dependent manner, and this effect lasted more than 1 day after the last drug administration. These data indicate that nerve ischemia plays an important role in maintaining the thermal hyperesthesia induced by nerve constriction injury in the rat.

Alprostadil↗
PubMed1993

Role of the injury discharge in the development of thermal hyperesthesia after sciatic nerve constriction injury in the rat.

BACKGROUND: Usually, a barrage of impulses ("injury discharge") is evoked following sensory nerve damage. It has been suggested that injury discharge may produce the hyperexcitatory state in the spinal cord, and this hyperexcitability may cause neurogenic pain. In the present study, the authors examined the role of injury discharge in developing the hyperesthetic state following nerve constriction injury. METHODS: A model of thermal hyperesthesia caused by a constriction injury created by making four loose ligations around the rat sciatic nerve was examined. To block the injury discharge, 0.5% bupivacaine was applied to the sciatic nerve before constriction injury. To block the hyperexcitatory state, (+)-MK-801, an N-methyl-D-aspartate antagonist, was administered intrathecally 15 min before the nerve lesion. RESULTS: Blocking injury discharge significantly delayed the development of hyperesthesia. Bupivacaine had no effect on the development of hyperesthesia when bupivacaine was applied to the sciatic nerve 15 min after the nerve constriction injury. Systemic bupivacaine had no effect on the development of thermal hyperesthesia. Intrathecal (+)-MK-801 also delayed the development of hyperesthesia when (+)-MK-801 was administered intrathecally 15 min before the nerve injury. When (+)-MK-801 was administered 15 min after the nerve injury, (+)-MK-801 had no effect on the development of hyperesthesia. CONCLUSION: These results suggest that injury discharge may induce facilitation of spinal dorsal horn neurons, and this spinal facilitation may play an important role in developing thermal hyperesthesia following sciatic nerve constriction injury.

Animals↗
PubMed2002

Prevalence of hyperesthesia detected by current perception threshold test in subjects with glucose metabolic impairments in a community.

OBJECTIVE: Recent studies reported that hyperesthesia may be an indicator of early diabetic polyneuropathy. Using the current perception threshold (CPT) test, which stimulates peripheral sensory nerve fibers by three different frequencies (2,000, 250, and 5 Hz), we investigated the relationship between hyperesthesia and glucose metabolic impairment in a community. METHODS: The number of subjects, aged 40 to 79 years, was 2,074. The CPT values at each frequency were classified into three categories (hyperesthesia, normal, and hypoesthesia). Subjects were also subgrouped into three groups (normal, insulin resistance, and diabetes) according to glucose metabolic status, and those with hypoesthesia at each frequency were excluded in the analyses. RESULTS: The prevalence of hyperesthesia at 2,000, 250, and 5 Hz in male diabetic subjects were 14.1, 15.6, and 7.7%, respectively, and 22.2, 24.5, and 16.4% respectively in female diabetic subjects. In logistic regression analysis adjusted for age, females with diabetes showed a significantly high odds ratio (OR) for hyperesthesia at 2,000 Hz (OR, 2.42; 95% confidence interval (95%CI), 1.18 to 4.97) and 250 Hz (OR, 2.65; 95%CI, 1.31 to 5.37). In male diabetic subjects, a significantly high odds ratio for hyperesthesia was seen at 250 Hz (OR, 2.09; 95%CI, 1.07 to 4.05). CONCLUSION: Our results suggested that hyperesthesia may emerge coupled with developing diabetes, supporting the precedent hypothesis.

Adult↗
PubMed1995

Role of nitric oxide in the development of thermal hyperesthesia induced by sciatic nerve constriction injury in the rat.

BACKGROUND: Nitric oxide (NO) has been shown to be involved in mediating nociceptive information transmission in the spinal cord. It is known that the N-methyl-D-aspartate receptor plays an important role in the development of the spinal facilitation evoked by a protracted small afferent input and that this effect is mediated at least in part by NO. Recently, it has been found that N-methyl-D-aspartate receptor-mediated spinal facilitation is crucial in the development of thermal hyperesthesia evoked by a nerve constriction injury. In the current study, we investigated the role of NO in the development of thermal hyperesthesia after a nerve constriction injury. METHODS: The Bennett and Xie model (four loose chromic gut ligations around the rat sciatic nerve) was used to examine the development of thermal hyperesthesia. An NO synthase inhibitor (N omega-nitro-L-arginine or N omega-nitro-L-arginine methyl ester hydrochloride), rat hemoglobin, or L-arginine was administered intrathecally 10 min before the nerve injury (pretreatment study) or 15 min after the nerve injury (posttreatment study). RESULTS: Pretreatment but not posttreatment administration of NO synthase inhibitor significantly delayed the development of thermal hyperesthesia. The effect of NO synthase inhibitor was reversed by the coadministration of L-arginine but not by the coadministration of D-arginine. Pretreatment with rat hemoglobin also delayed the development of thermal hyperesthesia. L-Arginine itself had no effect on the development of thermal hyperesthesia. CONCLUSIONS: NO may play an important role in the development of N-methyl-D-aspartate receptor-mediated spinal facilitation after a nerve constriction injury.

Animals↗
PubMed1989

Role of spinal adenosine receptors in modulating the hyperesthesia produced by spinal glycine receptor antagonism.

The intrathecal administration of strychnine in rats yields a prominent touch-evoked allodynia. The effects of an intrathecally administered A1 adenosine agonist: N6-(L-2-phenylisopropyl)-adenosine (LPIA) or an A2 adenosine agonist: 5'-(N-ethyl carboxamido)-adenosine (NECA), on this touch-evoked hyperesthesia were examined. Over the range of 0.3-1.0 nmol these agents produced a dose-dependent inhibition of the strychnine-evoked hyperesthesia. This inhibition was reversed following intraperitoneal injection of caffeine, an adenosine receptor antagonist. No statistical differences between LPIA and NECA were recorded. The powerful effect of adenosine analogues on strychnine hyperesthesia occur at doses that have only a mild analgesic effect on the thermally evoked hot-plate response. This effect is in contrast to opioids, which have been reported to be only minimally effective against strychnine-evoked hyperesthesia. The characteristics of the strychnine hyperesthesia appear to mimic the clinical phenomenon observed in patients suffering from sensory dysesthesia following nerve injury and suggest a possible role for the adenosine receptor in certain pain states.

Animals↗
PubMed2004

Central representation of muscle pain and mechanical hyperesthesia in the orofacial region: a positron emission tomography study.

Functional neuroimaging studies of the human brain have revealed a network of brain regions involved in the processing of nociceptive information. However, little is known of the cerebral processing of pain originating from muscles. The aim of this study was to investigate the cerebral activation pattern evoked by experimental jaw-muscle pain and its interference by simultaneous mechanical stimuli, which has been shown to evoke hyperesthesia. Ten healthy subjects participated in a PET study and jaw-muscle pain was induced by bolus injections of 5% hypertonic saline into the right masseter muscle. Repeated von Frey hair stimulation (0.5 Hz) of the skin above the masseter muscle was used as the mechanical stimulus. Hypertonic saline injections caused strong muscle pain spreading to adjacent areas. von Frey stimulation was rated as non-painful but produced hyperesthesia during jaw-muscle pain. Jaw-muscle pain was associated with significant increases in regional cerebral blood flow (rCBF) in the dorsal-posterior insula (bilaterally), anterior cingulate and prefrontal cortices, right posterior parietal cortex, brainstem, cavernous sinus and cerebellum. No rCBF changes occurred in primary or secondary somatosensory cortices. In contrast, von Frey stimulation produced a significant rCBF increase in the contralateral SI face representation. Mechanical hyperesthesia was associated with significant rCBF increases in the subgenual cingulate and the ventroposteromedial and dorsomedial thalamus. These results suggest that the cerebral processing of jaw-muscle pain may differ from the processing of cutaneous pain and that mechanical hyperesthesia, which often is encountered in clinical cases, has a unique representation in the brain.

Adult↗
PubMed1993

The effects of morphine, MK-801, an NMDA antagonist, and CP-96,345, an NK1 antagonist, on the hyperesthesia evoked by carageenan injection in the rat paw.

BACKGROUND: The spinal mechanisms underlying the hyperesthetic state during inflammation are little understood. To gain a better understanding of these mechanisms, this study evaluated the effects of intrathecal morphine; MK-801, an N-methyl-D aspartic (NMDA) antagonist; and CP-96,345, an NK1 antagonist, on the hyperesthesia observed after carageenan injection of the rat paw. METHODS: In rats injected with 2 mg carageenan, the paw withdrawal latency (PWL) for the injected paw was typically 5-6 s less than that for the untreated paw, at 2 h after the carageenan injection. Drugs were administered 2 h after the carageenan injection. The magnitude of hyperesthesia was evaluated with the difference score (DS), which was calculated by subtracting the PWL of the untreated paw from the PWL of the injected paw. RESULTS: Intrathecal morphine increased PWLs of both the injected and the untreated paws equally in a dose-dependent manner, but intrathecal morphine did not affect the level of DS. Intrathecal MK-801 increased PWLs of the injected paw to the level of the untreated paw in a dose-dependent manner and increased the DS levels. Intrathecal CP-96,345 had no effect on PWLs of either the injected or the untreated paw. Coadministration of MK-801 with morphine reduced the DS for each dose of morphine. CONCLUSIONS: These data indicate that (1) an NMDA receptor, but not an NK1 receptor, plays an important role in maintaining the hyperesthesia after carageenan injection; and (2) NMDA antagonism has a simple additive interaction with morphine in the carageenan model of inflammatory hyperesthesia.

Animals↗
PubMed1993

The role of focal nerve ischemia and Wallerian degeneration in peripheral nerve injury producing hyperesthesia.

BACKGROUND: A new model of pain associated with an experimental peripheral mononeuropathy has stimulated interest in mechanisms of pain and their structural correlates in peripheral nerve, the site of the experimental lesion. METHODS: The pathology of the neuropathy was studied and the results correlated with alterations in nerve blood flow and with the behavioral response to heat applied to the foot. The focal neuropathy was created by loosely tying several ligatures around rat sciatic nerve, which produces hyperesthesia in the ligated limb in 3-5 days. The neuropathology was striking with epineurial and endoneurial vascular stasis, edema, and extensive nerve fiber injury in the ligated segment noted at 1 week after ligation. RESULTS: Nerve blood flow was reduced significantly in the ligated segment during the development of the hyperesthesia response, suggesting that changes in nerve blood flow caused by the ligature compression of the epineurial vessels contributes to the nerve fiber injury and pathophysiology of the model. To further test this hypothesis, the epineurial vasculature was removed from 1-cm lengths of rat sciatic nerve, which reduces nerve blood flow by 58%, and by ligation of the ipsilateral femoral artery, which focally reduces nerve blood flow by 70%, and the behavioral response to heating of the paw was evaluated at 1 week. Crush injury was used as a positive control creating Wallerian degeneration without a substantial reduction in nerve blood flow. CONCLUSIONS: The results suggest that ischemia is an important initial pathogenic mechanism in the hyperesthesia associated with the loose ligature pain model, in so far as it produces Wallerian degeneration and axonal injury. Modest degrees of ischemia producing only demyelination did not produce significant hyperesthesia.

Animals↗
PubMed1994

Time-dependent effect of morphine and time-independent effect of MK-801, an NMDA antagonist, on the thermal hyperesthesia induced by unilateral constriction injury to the sciatic nerve in the rat.

BACKGROUND: It is known that peripheral nerve injury induces time-dependent changes in dorsal horn function. The current study investigated the time dependency of the effects of intrathecal morphine and MK-801, an N-methyl-D-aspartate antagonist, on the thermal hyperesthesia evoked by unilateral constriction injury to the sciatic nerve in the rat. METHODS: In rats with a unilateral constriction injury to the sciatic nerve, paw withdrawal latency against thermal stimulation for the injured paw was typically 3 s less than that for the uninjured paw during the first 5 weeks after the injury. Drugs were administered intrathecally 1 or 5 weeks after the nerve injury. RESULTS: Intrathecal morphine increased the paw withdrawal latencies of both the injured paw and the uninjured paw in an equally dose dependent manner in the 1-week study. In the 5-week study, morphine increased the paw withdrawal latency of the uninjured paw in a dose-dependent manner, but not that of the injured paw. Intrathecal MK-801 increased the paw withdrawal latency of the injured paw to the level of the uninjured paw in a dose-dependent manner in both the 1- and 5-week studies. CONCLUSIONS: These data indicate that (1) an N-methyl-D-aspartate receptor-mediated spinal facilitation may be the common mechanism maintaining the thermal hyperesthesia evoked by the constriction injury, and (2) the effects of intrathecal morphine on this thermal hyperesthesia are time-dependent.

Animals↗
PubMedDate not supplied

[Indices characterizing the expression of hyperesthesia of the hard dental tissues in patients with periodontitis].

Clinical examinations of 226 patients with periodontitis have revealed in 61% of them hyperesthesia of the hard dental tissues, that was mostly generalized, characterized by a marked reaction to thermal, chemical, and tactile stimulants. Study of the mineral metabolism has demonstrated that growing bone tissue loss in dental biopsy specimens and gingival fluid is associated with reducing levels of P, Ca, and Mg. Combination of clinical manifestations of periodontitis and hyperesthesia necessitate search for combined therapy aimed at simultaneous elimination of hyperesthesia and inflammation.

Adult↗
PubMed1990

A-fibers mediate mechanical hyperesthesia and allodynia and C-fibers mediate thermal hyperalgesia in a new model of causalgiform pain disorders in rats.

Unilateral tight ligation of about half of the sciatic nerve in rats rapidly produces sympathetically dependent neuropathic pain which lasts many months and resembles causalgia in humans. The sensory abnormalities detected at the plantar side of the hindpaws include: (1) nocifensive responses to repetitive light touch (allodynia); (2) bilateral reduction in withdrawal thresholds to repetitive von-Frey hair stimulation (mechanical hyperesthesia); (3) bilateral reduction in withdrawal thresholds to CO2 laser heat pulses; and (4) unilateral increase in response duration to an intense laser heat pulse (thermal hyperalgesia). Using neonatal capsaicin treatment, we determined the type of afferent fiber remaining in the partially injured nerve, which mediates these disorders. Capsaicin, which destroys most C- and some A delta-fibers in peripheral nerves, had no effect on the touch-evoked allodynia and mechanical hyperesthesia that are produced by partial sciatic nerve injury. These disorders were, therefore, mediated by myelinated fibers. In contrast, thermal hyperalgesia failed to develop in capsaicin-treated rats following partial nerve injury. Thus, thermal hyperalgesia produced by partial nerve injury appears to be mediated by heat-nociceptive C-fibers.

Afferent Pathways↗
PubMed2006

[Investigation of visceral hyperesthesia in irritable bowel syndrome].

BACKGROUND: It has been well established that visceral hyperesthesia plays a role in the development of irritable bowel syndrome (IBS). AIMS: 1. to detect the possible changes of visceral perception in different subtypes of IBS patients, 2. to analyze the difference of visceral hyperaesthesia in different subtypes of IBS, 3. to examine whether distension protocols (e.g. phasic or ramp distension) has any influence on sensory thresholds, 4. to analyze the differences of perception thresholds produced by phasic or ramp distension in different subtypes of IBS. METHODS: 10 patients having colorectal polypectomy (control group) and 40 IBS patients were studied. The diagnosis was based on the Rome-II criteria. Diarrhoea-predominant, alternating and constipation-predominant subtypes were determined by the Talley bowel habit questionnaire. Sensory thresholds were detected by semi random ascending phasic and ramp rectosigmoid distension. Rectal dynamic compliance was calculated by using the dV/dP ratio. RESULTS: 1. The pain thresholds determined by phasic distension were significantly lower in all subtypes of IBS. 2. Increased thresholds for pain were found in almost half of constipation-predominant IBS patient determined by ramp distension. Thus two distinct subgroups could be found based on the findings of ramp distension: a normosensitive and a hyposensitive group. 3. Rectal dynamic compliance was significantly higher both in the constipation-predominant and alternating subtype of IBS patients. CONCLUSION: Visceral hyperesthesia can be detected in all types of IBS. Tolerance to physiologic stimuli could be observed in constipating IBS patients that is not related to the increase of rectal compliance.

Adult↗
PubMed1992

Studies on the spinal interaction of morphine and the NMDA antagonist MK-801 on the hyperesthesia observed in a rat model of sciatic mononeuropathy.

This study evaluated the effects of intrathecally coadministered morphine and the N-methyl-D-aspartate (NMDA) antagonist (+)5-methyl-10,11-dihydro-5H- dibenzocyclohepten-5,10-imine maleate (MK-801) on the thermally evoked hindpaw withdrawal latency (PWL) in rats with one paw (ipsilteral) rendered hyperesthetic by the unilateral application of loose ligatures to the sciatic nerve (delta PWL (+/- S.D.) = PWLhyperesthetic paw - PWLnormal paw = -3.1 +/- 1.2 s). Intrathecal morphine produced a dose-dependent (0.1-10 micrograms; P less than 0.0001) elevation in the thermal response latency of both the contralateral (normal) and ipsilateral (hyperesthetic) paw. delta PWL did not vary with morphine, indicating that the dose-response curves were parallel but shifted to the right for the hyperesthetic paw. For the normal paw, MK-801 (10 micrograms) was without effect upon the response latency; whereas, the response latency of the hyperesthetic paw was elevated to the same as the normal paw, i.e. the hyperesthesia was selectively abolished (delta PWL (+/- S.D.) = -0.067 +/- 2.73). Co-administration of MK-801 with morphine did not alter the effects of morphine in the normal paw, but reduced the delta PWL for each dose of morphine. These results suggest that NMDA antagonism (1) does not alter the thermal sensitivity in the normal paw, (2) selectively abolishes the hypersensitivity of the hypersthetic paw and (3) has a simple additive interaction with the antinociceptive effects of morphine in the hyperesthetic paw.

Animals↗
PubMed1998

Tactile hyperesthesia, altered epidermal innervation and plantar nerve injury in the hindfeet of rats housed on wire grates.

The effects of wire grates on nerve injury and recovery were examined in rats housed in cages with sawdust-covered solid flooring. For the first 3 weeks of the study, 20 rats were housed on sawdust alone and 20 rats were housed in cages with wire grates placed over the sawdust. For the remaining 9 weeks, 10 animals housed on sawdust had wire grates added to their cages, while grates were removed from the cages of 10 animals. The effects of tactile stimulation on hindpaw plantar skin was measured weekly using the Von Frey filament test. Intraepidermal innervation using PGP 9.5 immunostaining and plantar nerve histology were assessed at the end of the 12-week study. After just 1 week on grates, hindpaw withdrawal thresholds were already markedly decreased and remained low until the grates were removed at 3 weeks. Thresholds returned to normal by 4 weeks after removal of the grates. Wire grates also induced increases in PGP 9.5 immunoreactive intraepidermal fine nerve endings that were normalized after grate removal. Demyelination, Wallerian degeneration and Renaut bodies were induced in the medial plantar nerve in rats housed in cages with wire-grate flooring. Nerve injury was largely resolved after 9 weeks on sawdust flooring. These data demonstrate that wire grates rapidly induce hindpaw tactile hyperesthesia and plantar neuropathy in rats and emphasize a risk of using wire-grate cage flooring in studies assessing hindlimb function and structure.

Animals↗
PubMed1986

High dose of spinal morphine produce a nonopiate receptor-mediated hyperesthesia: clinical and theoretic implications.

In rats with chronically implanted intrathecal catheters, high concentrations of morphine (3 microliters of 50 mg/ml: 150 micrograms) yielded a reliable and striking syndrome of pain behavior that involved intermittent bouts of biting and scratching at the dermatomes innervated by levels of the spinal cord proximal to the catheter tip. In addition, during intervals between bouts of agitation, the animals displayed a clear, marked hyperesthesia where an otherwise innocuous stimuli (brush stroke) evoked significant signs of discomfort and consequent aggressive behavior. These effects were exaggerated rather than reversed by high doses of naltrexone. The effect, perfectly mimicked by a considerably lower dose of morphine-3-glucuronide (15 micrograms) or the glycine antagonist strychnine (30 micrograms), was not produced by equimolar concentrations of sodium sulfate, glucuronide, methadone, or sufentanil. In halothane-anesthetized cats, light brushing of the hindpaw and tail or low-intensity stimulation of the sciatic nerves resulted in prominent elevations in blood pressure and pupil diameter following the intrathecal administration of high concentrations (50 mg/ml; 0.1 ml) of morphine sulfate. This effect, exaggerated by naloxone, was produced by a lower concentration of intrathecal morphine-3-glucuronide (5 mg/ml; 0.1 ml) but not by intrathecal saline. These results suggest the possibility that the effects of high doses of morphine may be characterized by a nonopiate receptor-mediated effect that alters the coding of sensory information in the spinal cord. The authors speculate that high concentrations of spinal opiates, as may be employed in tolerant terminal-cancer patients, could exert an action that physiologically antagonizes the analgesic effects otherwise mediated by the action of morphine on the spinal opiate receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Spinal↗
PubMed1993

Pathology of experimental compression neuropathy producing hyperesthesia.

An experimental neuropathy in rats produced by tying loosely constrictive ligatures around one sciatic nerve has recently been shown to produce pain-related behavior that follows a reproducible time course. In the present study, we assessed the degree of thermal hyperesthesia and examined the sciatic nerves by light and electron microscopy at different time points from 1 day to 12 weeks after surgery. Edema was the initial pathologic change seen in the neuropathy and was associated with early Wallerian degeneration on day 1. Injury to the connective tissue sheaths with interruption of the perineurial layer, infiltration of macrophages into the endoneurium, and proliferation of endothelial cells were observed during the first week. Endothelial cells hypertrophied and changed to a rhomboid shape with gaps between adjacent cells. Most large myelinated and many small myelinated fibers underwent Wallerian degeneration. Unmyelinated fiber numbers were reduced to one-third of the normal value from day 5 to day 14. Axonal sprouts were numerous after 1 week and grew into the segment distal to the ligatures by 4 weeks. Aberrant sprouts in minifascicles outside the perineurium were present from 4 weeks on. The original ligatures were rapidly surrounded by large amounts of fibrous tissue and mostly absorbed by 12 weeks; the initial fascicular compression caused by the ligatures was maintained by the fibrous tissue. We conclude that, whereas neuroma formation may contribute to the pain-related behavior in the later stages of this neuropathy, acute changes in the endoneurial microenvironment are important for its initial development.

Animals↗