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Biomedical subjects

W S Kingery

Publications and source records attributed to W S Kingery.

At least 19 recordsLinked to original sources
PubMed2001

Glucocorticoid inhibition of neuropathic limb edema and cutaneous neurogenic extravasation.

Sciatic nerve section in rats evokes chronic limb edema, pain behavior, and hindpaw hyperalgesia, a syndrome resembling the complex regional pain syndrome type II (CRPS II or causalgia) in man. Glucocorticoids such as methylprednisolone (MP) have been used as analgesic and anti-edematous agents in patients suffering from CRPS, and interestingly these therapeutic effects appear to persist in some patients after stopping the medication. Similar to the CRPS clinical response to glucocorticoids, we now demonstrate that chronic hindpaw edema in the sciatic transection CRPS model is reversed by a continuous infusion of MP (3 mg/kg/day over 21 days), and this anti-edematous effect persists for at least 1 week after discontinuing MP. Furthermore, there is a chronic increase in spontaneous protein extravasation in the hindpaw skin of rats after sciatic transection, similar to the increased protein extravasation observed in the edematous hands of CRPS patients. A 2-week infusion of MP (3 mg/kg/day) reduced spontaneous protein extravasation in the hindpaw skin by 80%. We postulated that increased spontaneous neurogenic extravasation resulted in development of limb edema in both the animal model and the CRPS patient, and that the anti-edematous effects of MP are due to an inhibition of spontaneous extravasation. Additional experiments examined the inhibitory effects of MP infusion on electrically-evoked neurogenic extravasation in the hindpaw skin of normal rats. MP inhibition was dose- and time-dependent, with an ED(50) of 1.2 mg/kg/day for a 14-day continuous infusion of MP, and a maximum inhibitory effect requiring 17 days of MP infusion (3 mg/kg/day). MP (3 mg/kg/day for 14 days) also blocked both capsaicin- and SP-evoked neurogenic extravasation, indicating a post-junctional inhibitory effect. Our interpretation is that increased spontaneous neurogenic extravasation in this CRPS model contributed to the development and maintenance of hindpaw edema, and that chronic MP administration dose- and time-dependently blocked neurogenic extravasation at a post-junctional level, thus reversing spontaneous extravasation and limb edema in this model.

Animals↗
PubMed2001

Enkephalin release and opioid receptor activation does not mediate the antinociceptive or sedative/hypnotic effects of nitrous oxide.

In previous studies using Fos expression as a marker of neuronal activation, we showed that nitrous oxide (N(2)O) activates bulbospinal noradrenergic neurons in rats and that destruction of these neuronal pathways leads to loss of N(2)O antinociceptive action. Based on previous rat studies it has been proposed that these noradrenergic neurons are activated through opioid receptors through the release of endogenous opioid ligands in the periaqueductal gray. Using mice with a disrupted preproenkephalin gene (Penk2 -/-) and the opioid receptor antagonist naltrexone, we investigated the role of enkephalinergic mechanisms and opioid receptor activation in the behavioral and bulbospinal neuron responses to N(2)O in mice. The antinociceptive response to N(2)O was investigated using the tail-flick, hot-plate, and von Frey assays, the sedative/hypnotic response was measured using rotarod and loss of righting reflex, and bulbospinal neuronal activation was assessed with pontine Fos immunostaining. No differences were observed between wild-type and Penk2 -/- mice for the antinociceptive, sedative/hypnotic, and pontine neuronal activation effects of N(2)O. Similarly, naltrexone did not block N(2)O-induced antinociception, sedation, or hypnosis. We conclude that neither enkephalin nor opioid receptors participate in either the antinociceptive or the sedative/hypnotic actions of N(2)O in mice.

Analgesics↗
PubMed2001

Glucocorticoid inhibition of neuropathic hyperalgesia and spinal Fos expression.

Glucocorticoids are used to treat patients suffering from neuropathic pain and complex regional pain syndromes (CRPS). Previously we found that once-daily injections of the glucocorticoid methylprednisolone had no antihyperalgesic effect in the rat sciatic nerve transection model for CRPS, but on the basis of CRPS clinical data, we hypothesized that a continuous infusion of methylprednisolone might prove effective. We further postulated that the antihyperalgesic effects of glucocorticoids were mediated by the inhibition of spinal neuron hyperactivity and by the depletion of substance P or its NK(1) receptor. This study tested the effects of continuously infused methylprednisolone in sciatic nerve-transected rats. Continuous infusion of methylprednisolone (3 mg. kg(-1). d(-1) for 21 days), started after the development of neuropathic hyperalgesia, reversed both heat and mechanical hyperalgesia over 2 wk, and this effect persisted for at least 1 wk after discontinuing methylprednisolone. In addition, continuous methylprednisolone infusion partially reversed nerve injury-evoked Fos expression in the dorsal horns, suggesting that glucocorticoids can inhibit the spinal neuron hyperactivity induced by chronic sciatic nerve transection. Finally, no changes were observed in spinal substance P or NK(1) immunoreactivity after chronic methylprednisolone infusion, suggesting that the depletion of this neuropeptide or its receptor does not contribute to the antihyperalgesic actions of glucocorticoids.

Animals↗
PubMed2000

Antinociceptive action of nitrous oxide is mediated by stimulation of noradrenergic neurons in the brainstem and activation of [alpha]2B adrenoceptors.

Although nitrous oxide (N(2)O) has been used to facilitate surgery for >150 years, its molecular mechanism of action is not yet defined. Having established that N(2)O-induced release of norepinephrine mediates the analgesic action at alpha(2) adrenoceptors in the spinal cord, we now investigated whether activation of noradrenergic nuclei in the brainstem is responsible for this analgesic action and which alpha(2) adrenoceptor subtype mediates this property. In rats, Fos immunoreactivity was examined in brainstem noradrenergic nuclei after exposure to nitrous oxide. After selective lesioning of noradrenergic nuclei by intracerebroventricular application of the mitochondrial toxin saporin, coupled to the antibody directed against dopamine beta hydroxylase (DbetaH-saporin), the analgesic and sedative actions of N(2)O were determined. Null mice for each of the three alpha(2) adrenoceptor subtypes (alpha(2A), alpha(2B), and alpha(2C)), and their wild-type cohorts, were tested for their antinociceptive and sedative response to N(2)O. Exposure to N(2)O increased expression of Fos immunoreactivity in each of the pontine noradrenergic nuclei (A5, locus coeruleus, and A7). DbetaH-saporin treatment eliminated nearly all of the catecholamine-containing neurons in the pons and blocked the analgesic but not the sedative effects of N(2)O. Null mice for the alpha(2B) adrenoceptor subtype exhibited a reduced or absent analgesic response to N(2)O, but their sedative response to N(2)O was intact. Our results support a pivotal role for noradrenergic pontine nuclei and alpha(2B) adrenoceptors in the analgesic, but not the sedative effects of N(2)O. Previously we demonstrated that the analgesic actions of alpha(2) adrenoceptor agonists are mediated by the alpha(2A) subtype; taken together with these data we propose that exogenous and endogenous alpha(2) adrenoceptor ligands activate different alpha(2) adrenoceptor subtypes to produce their analgesic action.

Analgesics↗
PubMed2000

The lumbar multifidus muscle in polysegmentally innervated.

We conducted a prospective case study to determine whether the lumbar multifidus muscle is polysegmentally innervated. A 49-year-old man with chronic mechanical low back pain underwent bilateral percutaneous radiofrequency neurotomy of the medial branches of the L3 dorsal rami. Electromyography (EMG) examination was performed in the L2-5 multifidi both prior to and 3 weeks after the procedure. Positive sharp waves and fibrillations appeared in the L3-L5 multifidi after the neurotomy. This study provides electrophysiological evidence in the human lumbar spine that the medial branch of the lumbar root innervates the multifidus muscle at multiple levels, i.e., the lumbar multifidus muscle is polysegmentally innervated. As a result, electromyography of the multifidus cannot identify a specific level of lumbar radiculopathy.

Denervation↗
PubMed1999

Opioidergic and adrenergic modulation of formalin-evoked spinal c-fos mRNA expression and nocifensive behavior in the rat.

Fos protein expression has been used to reflect neuronal activation in pain processing pathways although analgesics may uncouple behavioral and Fos responses. We determine whether formalin-induced spinal c-fos mRNA expression (Northern blotting) correlates with nocifensive behavior following pretreatment with morphine, the alpha2-adrenoceptor agonist dexmedetomidine, or their respective antagonists naloxone and atipamezole. Both opiate and alpha2-adrenoceptor agonists reduced formalin-induced c-fos gene transcription and nocifensive behavior via their cognate receptors. Unexpectedly, blockade of either the opiate or alpha2-adrenergic receptors, alone, caused an increase in formalin-evoked c-fos mRNA; while blocking the opiate receptor had no effect on formalin-induced behavior, alpha2-adrenoceptor block had an analgesic effect, indicating discordance between c-fos message transcription and nocifensive behavior. We concluded that the formalin-induced spinal c-fos signal was a poor predictor of the behavioral response to pharmacological manipulation of pain processing pathways.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1999

Nitrous oxide produces antinociceptive response via alpha2B and/or alpha2C adrenoceptor subtypes in mice.

BACKGROUND: Opiate receptors in the periaqueductal gray region and alpha2 adrenoceptors in the spinal cord of the rat mediate the antinociceptive properties of nitrous oxide (N2O). The availability of genetically altered mice facilitates the detection of the precise protein species involved in the transduction pathway. In this study, the authors establish the similarity between rats and mice in the antinociceptive action of N2O and investigate which alpha2 adrenoceptor subtypes mediate this response. METHODS: After obtaining institutional approval, antinociceptive dose-response and time-course to N2O was measured in wild-type and transgenic mice (D79N), with a nonfunctional alpha2A adrenoceptor using tail-flick latency. The antinociceptive effect of N2O was tested after pretreatment systemically with yohimbine (nonselective alpha2 antagonist), naloxone (opiate antagonist), L659,066 (peripheral alpha2-antagonist) and prazosin (alpha2B- and alpha2C-selective antagonist). The tail-flick latency to dexmedetomidine (D-med), a nonselective alpha2 agonist, was tested in wild-type and transgenic mice. RESULTS: N2O produced antinociception in both D79N transgenic and wild-type litter mates, although the response was less pronounced in the transgenic mice. Antinociception from N2O decreased over time with continuing exposure, and the decrement was more pronounced in the transgenic mice. The antinociceptive response could be dose dependently antagonized by opiate receptor and selective alpha2B-/alpha2C-receptor antagonists but not by a central nervous system-impermeant alpha2 antagonist (L659,066). Whereas dexmedetomidine exhibited no antinociceptive response in the D79N mice, the robust antinociceptive response in the wild-type litter mates could not be blocked by a selective alpha2B-/alpha2C-receptor antagonist. CONCLUSION: These data confirm that the antinociceptive response to an exogenous alpha2-agonist is mediated by an alpha2A adrenoceptor and that there appears to be a role for the alpha2B- or alpha2C-adrenoceptor subtypes, or both, in the analgesic response to N2O.

Analgesics, Non-Narcotic↗
PubMed1998

The analgesic potency of dexmedetomidine is enhanced after nerve injury: a possible role for peripheral alpha2-adrenoceptors.

UNLABELLED: This study investigated the analgesic potency and site of action of systemic dexmedetomidine, a selective alpha2-adrenoceptor (alpha2AR) agonist, in normal and neuropathic rats. Ligation of the L5-6 spinal nerves produced a chronic mechanical and thermal neuropathic hyperalgesia in rats. von Frey fibers and a thermoelectric Peltier device were used to measure mechanical and heat withdrawal thresholds over the hindpaw. Systemic dexmedetomidine dose-dependently increased the mechanical and thermal thresholds in the control animals (50% effective dose [ED50] 144 and 180 microg/kg intraperitoneally [i.p.], respectively). Neuropathic animals responded to much smaller doses of dexmedetomidine with mechanical and thermal ED50 values of 52 and 29 microg/kg i.p., respectively. There was no difference between the control and neuropathic animals with respect to dexmedetomidine-evoked sedation, as determined by decreased grid crossings in an open-field activity chamber (ED50 12 and 9 microg/kg i.p., respectively). Atipamezole, a selective alpha2AR antagonist, blocked the analgesic and sedative actions of dexmedetomidine inboth the neuropathic and control animals. However, L-659,066, a peripherally restricted alpha2AR antagonist, could only block the analgesic actions of dexmedetomidine in the neuropathic rats, with no effect in control animals. In conclusion, nerve injury enhanced the analgesic but not the sedative potency of systemic dexmedetomidine and may have shifted the site of alpha2 analgesic action to outside the blood-brain barrier. IMPLICATIONS: We tested the analgesic efficacy of the alpha2 agonist dexmedetomidine in normal and nerve-injured rats. The analgesic potency of dexmedetomidine was enhanced after nerve injury with a site of action outside the central nervous system. Peripherally restricted alpha2 agonists may be useful in the management of neuropathic pain.

Adrenergic alpha-Agonists↗
PubMed1995

An EMG case report of lead neuropathy 19 years after a shotgun injury.

The clinical picture of lead neuropathy was classically described as a painless progressive motor neuropathy with axonal loss. The literature review fails to demonstrate a consensus on the site of axonal loss. This is an EMG report of a patient who developed a late lead neuropathy after a shotgun injury. A 69-year-old Filipino, healthy, male nondrinker sustained a shotgun injury to his left elbow. Nineteen years later he developed abdominal pain, followed by generalized weakness, distal greater than proximal in the extremities, and impaired pin-prick, proprioception, and two-point discrimination. He became nonambulatory and totally dependent in daily activities. He was lost to follow-up for 2 years until January 1993 when he presented with a blood lead level of 84 micrograms/dL. EMG examination revealed a sensorimotor peripheral polyneuropathy with severe axonal loss. This case demonstrates that axonal loss is the predominant feature in lead neuropathy and the location of pathology is in the peripheral nerves.

Action Potentials↗
PubMed1994

The natural resolution of a lumbar spontaneous epidural hematoma and associated radiculopathy.

This is a report of a 37-year-old man who, while lifting a heavy box, developed severe low-back pain radiating into the right anterior thigh. The only clinical signs were paraspinal muscle spasm and a positive femoral nerve stretch test on the right. An electromyographic study demonstrated denervation in the right L2, L3, and L4 myotomes and paraspinal muscles. Magnetic resonance imaging (MRI) showed a large L1-2 anterior epidural hematoma compressing the spinal cord. The patient's pain gradually improved with conservative management and he returned to light work after 4 weeks. Repeat electromyographic and MRI studies were normal, indicating a resolution of the radiculopathy and hematoma. The diagnosis and management of spontaneous epidural hematomas are discussed.

Adult↗
PubMed1993

The absence of brachial plexus injury in stroke.

Brachial plexus injury and proximal mononeuropathy have been reported as a potential complications in the hemiplegic shoulder after a stroke. The diagnosis of brachial plexus injury and proximal mononeuropathy in the hemiplegic extremity is complicated by the upper motor neuron findings on physical examination and by the diffusely abnormal electrodiagnostic test results frequently seen in hemiplegic limbs. This study investigated the incidence of brachial plexus injury and proximal mononeuropathy after a thromboembolic stroke. Hemiplegic patients (n = 50) underwent physical examination, needle electromyography of the hemiplegic extremities and nerve conduction studies across the brachial plexus within 4 months after a stroke. Combining the physical examination and electromyographic findings we were unable to make a diagnosis of brachial plexus injury or proximal mononeuropathy in any hemiplegic patient. Spontaneous electromyographic activity was observed in 68% of the arms and 70% of the legs examined on the hemiplegic side. The severity and incidence of spontaneous activity was evenly distributed in upper and lower trunk muscles. Mean central latencies across the lower brachial plexus were slightly delayed (12.5 +/- 2 v 11.6 +/- 2.2 ms, P < 0.01) compared with the contralateral normal limb, but in no case was the F wave unilaterally unelicitable. The mean hypothenar compound muscle action potential amplitude was diminished (7 +/- 2.7 v 9.2 +/- 4.1 mV, P < 0.01) in the hemiplegic hand compared with the normal side and the degree of amplitude loss inversely corresponded (r = -0.6, P < 0.01) to the amount of spontaneous electromyographic activity observed in the first dorsal interosseus muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1993

Temperature correction factors derived from normal subjects may be invalid in demyelinating neuropathies.

This study investigates the temperature effect on motor nerve conduction velocity (MNCV) in patients with neuropathic processes. Fourteen subjects, ages 18-77 yr old, with a diagnosis of uremic polyneuropathies (UPN, n = 5), diabetic polyneuropathies (DPN, n = 6) or carpal tunnel syndrome (CTS, n = 3) and ten normal controls were studied. After limb cooling in a cold water bath for 30 min, skin temperatures were sequentially obtained from the volar midwrist. Motor conduction velocities were obtained at 2-3 degrees increments between 22 and 33 degrees C. Results indicated a large individual variability; 0.1 to 1.8 in the median and 0.8 to 2.0 m/s/degrees C in the ulnar nerve when all three groups are considered together. There was a significant difference between the correction factors for control v DPN and control v CTS. A significant difference was also present for UPN v DPN and UPN v CTS (p < 0.05). There was a positive correlation (r = 0.746, p = 0.0001) between the baseline conduction velocities and the size of the correction factors in all the subjects. The effect of temperature on MNCV appears to be inversely correlated with the severity of conduction slowing or demyelination. These findings suggest that the use of a correction factor may be invalid when studying a demyelinated nerve, and that the extremity should be warmed to a specific temperature before an electrodiagnostic study.

Adolescent↗
PubMed1991

Adjacent neuropathic hyperalgesia in rats: a model for sympathetic independent pain.

Following sciatic nerve section in rats a saphenous nerve mediated adjacent neuropathic hyperalgesia (ANH) develops in response to pressure. This study demonstrates that a similar ANH to heat stimuli develops over the medial dorsum of the hindpaw (MDH) following sciatic section. A similar neuropathic hyperalgesia, with an associated pain syndrome, is seen in man following peripheral nerve section. When chronic bilateral ANH rats were unilaterally injected intradermally over the MDH with noradrenaline (NA), and with vehicle over the contralateral MDH, no side to side pressure or heat withdrawal threshold differences were observed. Likewise, no changes in pressure or heat withdrawal thresholds occurred in chronic ANH rats following chemical sympathectomy with 6-hydroxydopamine (6-OHDA). A similar pattern was seen in control rats treated with NA and 6-OHDA. The pressure and heat ANH seen in the rat was not dependent on sympathetic outflow, and thus provides an animal model for sympathetic independent pain (SIP). Sympathetic modulation was also ineffective on control rat nociceptive thresholds, which is in agreement with prior behavioral findings (Nature, 323 (1986) 158-160).

Animals↗
PubMed1988

Diminished dorsal root GABA sensitivity following chronic peripheral nerve injury.

The depolarizing effect of gamma-aminobutyric acid (GABA) on rat lumbar dorsal roots was studied in a sucrose gap chamber following axotomy or crush injury of the sciatic nerve or dorsal root. The mean depolarization elicited by GABA on normal dorsal roots (3.96 +/- 0.71 mV, N = 14) was significantly reduced following chronic sciatic axotomy (2.02 +/- 0.99 mV, N = 15). Chronic sciatic crush injury had no significant effect on dorsal root GABA sensitivity. The amplitudes of the dorsal root compound action potentials were the same from rats with normal and injured sciatic nerves, indicating that axons proximal to the sciatic nerve lesion did not undergo appreciable degeneration. A marked loss of dorsal root GABA sensitivity was also seen following dorsal root axotomy or crush injury (1.02 +/- 0.98 mV (N = 10) and 0.69 +/- 0.70 mV (N = 9), respectively). These results indicate that GABA sensitivity of dorsal roots is attenuated following peripheral nerve lesions in which regeneration and functional reconnection with peripheral targets are prevented. Previous work indicates that the primary afferent depolarization is reduced under similar conditions. The reduction in GABA sensitivity of dorsal root fibers described here may have a contributory role in the reduced primary afferent depolarization that follows peripheral nerve transection, which has pathophysiologic implications in chronic pain syndromes.

Action Potentials↗
PubMedDate not supplied

Electromyographic motor Tinel's sign in ulnar mononeuropathies at the elbow.

A novel test for localizing ulnar mononeuropathies (UM), the electromyographic (EMG) motor Tinel's sign, has been developed. While recording with a monopolar needle from the abductor digiti minimi, the ulnar nerve is lightly rolled at multiple sites across the elbow, and the test is considered positive if a burst of EMG activity is observed simultaneously with nerve compression. To determine the use of the EMG Tinel's sign, we evaluated 70 control nerves and 50 clinically suspected UMs. The EMG Tinel's sign had a 78% sensitivity and a 79% specificity for suspected UM at the elbow. The clinical Tinel's sign was present in 68% of suspected UM cases, and the combined sensitivity of the EMG and clinical Tinel's sign was 96%. Using nerve conduction study (NCS) values derived from the control nerves, 62% of UM nerves had abnormal NCS/EMG findings, and 28% of UM nerves had NCS/EMG abnormalities that could be localized to the elbow. The development of motor axon mechanosensitivity at the site of nerve injury is a new finding, not previously observed in electrophysiologic studies of animal nerve injury models or reported in the electrodiagnostic literature.

Action Potentials↗