Biomedical subjects

V Chapman

Publications and source records attributed to V Chapman.

At least 19 recordsLinked to original sources

PubMed2000

Spinal anandamide inhibits nociceptive transmission via cannabinoid receptor activation in vivo.

The endocannabinoid anandamide has affinity for cannabinoid and vanilloid receptors, which have opposing effects on nociceptive transmission. Effects of spinal administration of anandamide on innocuous and noxious evoked spinal neuronal responses in non-inflamed and carrageenin-inflamed rats were studied. Anandamide (0.1-50 microg/50 microl) had inconsistent effects in non-inflamed rats. Following carrageenin inflammation, anandamide (50 microg/50 microl) significantly reduced evoked neuronal responses, C-fibre mediated non-potentiated and post-discharge responses of neurones reduced to 65 +/- 5% and 57 +/- 10% of control, respectively. Effects of anandamide were blocked by SR141716A, a selective CB1 receptor antagonist. Spinal SR141716A (0.001-1 ng/50 microl) alone did not influence neuronal responses in inflamed rats. Spinal anandamide inhibited nociceptive transmission via CB1 receptors; following inflammation there is evidence for a loss of spinal endogenous cannabinoid tone.

Animals↗

PubMed2000

Effects of ENU dosage on mouse strains.

The germline supermutagen, N-ethyl-N-nitrosourea (ENU), has a variety of effects on mice. ENU is a toxin and carcinogen as well as a mutagen, and strains differ in their susceptibility to its effects. Therefore, it is necessary to determine an appropriate mutagenic, non-toxic dose of ENU for strains that are to be used in experiments. In order to provide some guidance, we have compiled data from a number of laboratories that have exposed male mice from inbred and non-inbred strains or their F(1) hybrids to ENU. The results show that most F(1) hybrid animals tolerate ENU well, but that inbred strains of mice vary in their longevity and in their ability to recover fertility after treatment with ENU.

Animals↗

PubMed2000

Visual risk factors for driving difficulty among older drivers.

This study sought to evaluate associations between visual function and self-reported difficulty with driving tasks. Drivers (N = 384) between the ages of 55 and 85 were selected from ophthalmology practices and optometry clinics; three out of four of the sample had cataracts and the remaining were cataract-free. Information on driving exposure and difficulty was obtained via self-report. Visual functional status of all participants was measured with respect to acuity, contrast sensitivity, disability glare and useful field of view. Cognitive impairment was evaluated using the Mattis Organic Mental Syndrome Screening Examination. The results show a pattern of difficulty in high-risk driving situations among those with decreased visual acuity and contrast sensitivity, even after adjustments for age, gender, weekly mileage, and cognitive impairment.

Age Factors↗

PubMed2000

Activation of spinal cannabinoid 1 receptors inhibits C-fibre driven hyperexcitable neuronal responses and increases [35S]GTPgammaS binding in the dorsal horn of the spinal cord of noninflamed and inflamed rats.

The analgesic potential of cannabinoid (CB) receptor agonists is of clinical interest. Improved understanding of the mechanisms of action of cannabinoids at sites involved in the modulation of acute and sustained inflammatory nociceptive transmission, such as the spinal cord, is essential. In vivo electrophysiology was used to compare the effect of the synthetic CB agonist, HU210, on acute transcutaneous electrical-evoked responses of dorsal horn neurons of noninflamed anaesthetized rats and anaesthetized rats with a peripheral carrageenin inflammation. CB receptor G-protein coupling in lumbar spinal cord sections of noninflamed and carrageenin-inflamed rats was studied with in vitro autoradiography of guanylyl 5'-[gamma-[35S]thio]triphosphate ([35S]GTPgammaS) binding. Spinal HU210 significantly inhibited the C-fibre-mediated late (300-800 ms) postdischarge response of dorsal horn neurons of noninflamed and carrageenin-inflamed rats; the CB1 receptor antagonist SR141716A blocked the effect of HU210. HU210 had limited effects on A-fibre-evoked dorsal horn neuronal responses of both groups of rats. HU210 significantly increased [35S]GTPgammaS binding in the dorsal horn of the spinal cord of both groups of rats compared with basal [35S]GTPgammaS binding; SR141716A blocked these effects. The predominant effect of spinal HU210, via CB1 receptor activation, was on the C-fibre driven postdischarge responses, a measure of neuronal hyperexcitability following repetitive C-fibre stimulation. Sustained, but not enhanced, antinociceptive effects of HU210 following carrageenin inflammation are reported; CB receptor G-protein coupling was not altered by inflammation. These results strengthen the body of evidence suggesting CB agonists may be an important novel analgesic approach for the treatment of sustained pain states.

Animals↗

PubMed2000

Neuronal inhibitory effects of methadone are predominantly opioid receptor mediated in the rat spinal cord in vivo.

This study aims to assess whether the antinociceptive actions of methadone are mediated solely through opioid mechanisms, or whether its reported affinity for NMDA receptors has physiological relevance in vivo. Methadone is a mu-opioid receptor agonist reported to relieve pain unresponsive to other opioids. It is a racemic mixture comprising d- and l-optical isomers; the d-isomer has a lower affinity for opioid receptors, and both also exhibit NMDA receptor binding, likely to indicate antagonist activity. d -Methadone is antinociceptive in behavioural studies via non-opioid mechanisms, which could include functional NMDA receptor-blocking activity. Here we investigate the ability of d - and dl -methadone to inhibit noxious and innocuous electrically-evoked responses of dorsal horn neurones in the anaesthetized rat. Racemic methadone (5, 25, 50, 250 microg) applied spinally, dose-relatedly inhibited the C-fibre evoked response, input and wind-up of the neurones, with a profile resembling that of morphine. d-Methadone (5, 25, 50, 250, 500 microg) was also inhibitory, although less potent by a factor of between 13 and 48 depending on the neuronal measure; its profile of inhibition resembled that of the racemic mixture rather than an NMDA receptor antagonist. Both compounds had minimal effects on Abeta-fibre-evoked activity. The inhibitory effects of both d - and dl -methadone on noxious-evoked activity were naloxone reversible. The naloxone reversibility of d -methadone inhibitions is best interpreted as indicative of a purely opioid mechanism of action. However, the ability of naloxone to reverse the effects of d -methadone may also reflect a degree of synergy between weak NMDA antagonist and opioid agonist activity.

Analgesics, Opioid↗

PubMed2000

Physiological properties of the lamina I spinoparabrachial neurons in the rat.

Single-unit extracellular recordings of spino-parabrachial (spino-PB) neurons (n = 53) antidromically driven from the contralateral parabrachial (PB) area were performed in the lumbar cord in anesthetized rats. All the spino-PB neurons were located in the lamina I of the dorsal horn. Their axons exhibited conduction velocities between 2.8 and 27.8 m/s, in the thin myelinated fibers range. They had an extremely low spontaneous activity (median = 0. 064 Hz) and a small excitatory receptive field (</=2 toes or pads). They were all activated by both peripheral A (mainly Adelta) and C fibers after intense transcutaneous electrical stimulation. Their discharge always increased in response to noxious natural stimuli of increasing intensities. The great majority (75%) of spino-PB neurons were nociceptive specific, i.e., they were excited only by noxious stimuli. The remaining (25%) still were excited primarily by noxious stimuli but also responded moderately to innocuous stimuli. Almost all spino-PB neurons (92%, 49/53) were activated by both mechanical and heat noxious stimuli. Among them, 35% were in addition moderately activated by noxious cold (thresholds between +20 and -10 degrees C). Only (8%, 4/53) responded exclusively to noxious heat. Spino-PB neurons clearly encoded the intensity of mechanical (n = 39) and thermal (n = 38) stimuli in the noxious range, and most of the individual stimulus-response functions were monotonic and positive up to 40/60 N. cm(-2) and 50 degrees C, respectively. For the mechanical modality, the mean threshold was 11.5 +/- 1.25 N. cm(-2) (mean +/- SE), the response increased almost linearly with the logarithm of the pressure between 10 and 60 N. cm(-2), the mean p(50) (pressure evoking 50% of the maximum response) and the maximum responsiveness were: 30 +/- 2.4 N. cm(-2) and 40.5 +/- 5 Hz, respectively. For the thermal modality, the mean threshold was 43.6 +/- 0.5 degrees C, the mean curve had a general sigmoid aspect, the steepest portion being in the 46-48 degrees C interval, the mean t(50) and the maximum responsiveness were: 47.4 +/- 0.3 degrees C and 40 +/- 4.4 Hz, respectively. Most of the spino-PB neurons tested (13/16) had their noxiously evoked responses clearly inhibited by heterotopic noxious stimuli. The mean response to noxious stimuli during heterotopic stimuli was 31.7 +/- 6.1% of the control response. We conclude that the nociceptive properties of the lamina I spino-PB neurons are reflected largely by those of PB neurons that were suggested to be involved in autonomic and emotional/aversive aspects of pain.

Action Potentials↗

PubMed1999

The effectiveness of spinal and systemic morphine on rat dorsal horn neuronal responses in the spinal nerve ligation model of neuropathic pain.

The treatment of pain arising from nerve injury can be difficult and the opioid sensitivity of neuropathic pain remains debatable. Clinical and animal studies report a wide range in the effectiveness of morphine, ranging from inadequate to potent analgesia. In this electrophysiological study we compare the effectiveness of spinal versus systemic administration of morphine on the natural and electrically evoked responses of spinal neurones of rats with a selective spinal nerve (L5/6) ligation. Recordings were made 1 week and/or 2 weeks after ligation. We have also compared the effects of morphine, by the two routes, on normal and sham operated animals. In spinal nerve ligated rats, morphine (0.1-5 microg) administered via the intrathecal route produced greater dose-dependent inhibitions of the neuronal responses compared with those produced by the systemic route (1-6 mg/kg). The dose response curves for intrathecal morphine on the C-fibre evoked and noxious natural stimuli evoked neuronal responses (mechanical and thermal) of spinal nerve ligated rats were to the left of those of sham operated and normal rats, suggesting an enhanced potency of intrathecal morphine after nerve injury. This was clearest for the lower doses of the opioid. The effects of spinal morphine on the responses to low intensity stimuli were similar in all groups of rats. In contrast to the spinal route, systemic morphine was less effective in inhibiting the evoked neuronal responses of spinal nerve ligated rats. This was especially clear for the C-fibre evoked and noxious natural stimuli evoked responses (mechanical and thermal) of spine nerve ligated rats. Our results suggest that the effectiveness of morphine may be partly related to the timing of the treatment relative to the duration of the neuropathy, the route of administration and also the neuropathic symptom. Spinal opioids may be a useful approach to pain control in neuropathic pain states where systemic routes produce inadequate analgesia.

Analgesics, Opioid↗

PubMed1999

The cannabinoid CB1 receptor antagonist, SR141716A, selectively facilitates nociceptive responses of dorsal horn neurones in the rat.

The effect of spinal administration of the selective cannabinoid CB1 receptor antagonist, SR141716A, and the selective CB2 receptor antagonist, SR144528, on innocuous versus noxious evoked responses of dorsal horn neurones in the spinal cord of the anaesthetized rat was investigated. SR141716A (0.001-1 ng 50 microl(-1)) dose-relatedly facilitated the non-potentiated component of the electrical C-fibre mediated neuronal response (120+/-6, 156+/-13, 192+/-33 and 192+/-31% of control respectively; n=6). In contrast, SR144528 (0.001-1 ng 50 microl(-1)) did not influence the non-potentiated component of the C-fibre evoked neuronal response (n=5). The electrical evoked Abeta-fibre mediated neuronal responses were not influenced by SR141716A or SR144528. The results of this study provide evidence that tonic cannabinoid CB1 receptor activation, but not CB2 receptor activation, attenuates acute nociceptive transmission, at the level of the spinal cord. These results suggest a selective antinociceptive role of the endogenous cannabinoids at spinal CB1 receptors.

Action Potentials↗

PubMed1999

Fire fatalities in older people.

OBJECTIVE: To compare the epidemiology of fire-related fatalities among older, middle-aged, and young people. DESIGN: Retrospective case series. SETTING: Alabama, 1992-1997. PARTICIPANTS: All persons fatally injured in fire-related incidents in the state of Alabama from 1992 to 1997. MEASUREMENTS: The State Fire Marshal's Office provided both demographic and autopsy information about the victim. In addition, information regarding the nature and circumstances of the fire was also obtained. RESULTS: Between 1992 and 1997, there were 674 fire-related deaths in the state of Alabama. The fire-related fatality rate was highest among older persons. The fatality rate was particularly high among older black people. The rate of fatal fires caused by heating devices was higher (15.0%) among older people compared with their young and middle-aged counterparts (6.3% and 4.5%, respectively). Fatalities among older people were least likely (26.0%) to occur if smoke detectors were present, compared with deaths among young and middle-aged persons (38.3% and 33.5%, respectively). There were fewer smoke detectors present in the fatal fires of older rural black adults and white adults (0.0% and 29.0%, respectively) compared with their urban counterparts (25.0% and 47.0%, respectively). Alcohol was not a factor in fatal fires involving older adults (29.0%) compared with those involving the young (52.0%) and middle-aged adults (73.9%). CONCLUSIONS: With the growth of the percentage of older people in the population, the problem of fire-related deaths in this age group is likely to increase. Interventions focused on this age group are necessary for the state of Alabama to meet the National Health Objectives for the year 2000.

Accidents↗

PubMed1998

Electrophysiological characterization of spinal neuronal response properties in anaesthetized rats after ligation of spinal nerves L5-L6.

1. Despite a number of models of nerve injury, few studies have examined how peripheral nerve injury influences spinal somatosensory processing. 2. Ligation of two (L5-L6) of the three spinal nerves that form the sciatic nerve produces a partial denervation of the hindlimb. Following ligation, rats exhibited withdrawal responses to normally innocuous punctate mechanical and cooling stimuli (acetone) applied to the lesioned hindpaw. Such mechanical and cooling allodynia was not observed in sham-operated rats. 3. A significantly greater proportion of spinal neurones of ligated rats exhibited spontaneous activity at post-operative (PO) days 7-10 (P = 0.03) and 14-17 (P = 0.0001), compared with sham controls. The frequency of the spontaneous activity was significantly higher than that of the sham controls (P = 0.03 and P = 0.02 for days 7-10 and days 14-17, respectively). 4. At the earlier PO period, significantly (P = 0.02) more neurones of spinal nerve-ligated (SNL) rats responded to brush compared with the sham controls; at the later PO period the proportion of neurones of SNL rats responsive to prod was significantly (P = 0.007) reduced compared with the sham controls. The magnitude of the evoked neuronal response of SNL rats at PO days 7-10 was comparable to that of the sham controls. The magnitudes of brush- and prod-evoked neuronal responses of SNL rats were significantly smaller (P = 0.05 and P = 0.002, respectively) than the sham controls at PO days 14-17. In addition, neuronal responses of SNL rats to mechanical punctate stimuli and the C fibre-evoked neuronal responses were significantly reduced at the later PO period, compared with sham controls. Abeta-fibre-induced wind-up was not observed under any conditions. 5. These complex changes in neuronal responses are both time and modality dependent. The plasticity of some of the neuronal and behavioural responses following nerve injury was difficult to reconcile. We suggest that an interplay between pathological peripheral and central mechanisms may account for some of the changes that could contribute to allodynia and hyperalgesia.

Acetone↗

PubMed1998

A case report of Usher's syndrome and anorexia nervosa.

OBJECTIVE: This report describes the rare combination of anorexia nervosa, deafness, and visual impairment with a particular emphasis on management issues. To the author's knowledge, this is the first report of an eating disorder in a patient who is deaf with a visual impairment. DISCUSSION: It describes the history of such a patient and the difficulties encountered in her treatment.

Adult↗

PubMed1998

Effects of systemic carbamazepine and gabapentin on spinal neuronal responses in spinal nerve ligated rats.

There are few pharmacological studies of central neuronal measures in animal models of neuropathic pain. In the present study we have compared the effects of two anticonvulsants, carbamazepine and gabapentin, on spinal neuronal responses of nerve injured rats (selective ligation of spinal nerves L5 and L6, SNL) and sham-operated rats. The development and maintenance of cooling and mechanical allodynia of the lesioned hindlimb of SNL rats was followed with behavioural indices. The contralateral hindlimb of SNL rats and the ipsilateral hindlimb of sham-operated rats did not develop allodynia. Electrophysiological studies of SNL rats were then performed at two post-operative (PO) time points (PO days 7-10 and PO days 14-17). Spinal neurones of SNL rats, but not sham-operated rats, exhibited spontaneous activity at both PO days 7-10 and 14-17 (1 +/- 0.4 and 3 +/- 1 Hz, respectively). Paradoxically, the magnitude of electrical (C-fibre) and natural (mechanical and thermal) evoked neuronal responses of SNL rats at PO days 14-17 were smaller than the evoked neuronal responses of SNL rats at PO days 7-10 and sham-operated rats. The electrical evoked A-fibre responses of neurones were comparable for the three groups of rats. Both subcutaneous carbamazepine (0.5-22.5 mg/kg) and gabapentin (10-100 mg/kg) significantly reduced the spontaneous activity of spinal neurones of SNL rats at both PO time points. Carbamazepine had inhibitory effects on electrical C- and A-fibre and mechanical punctate (9 and 50 g) evoked neuronal responses of SNL rats which were significantly different to the lack of effect of carbamazepine on these measures in sham-operated rats. Gabapentin had comparable effects as carbamazepine on the electrical C-and A-fibre and mechanical punctate (9 and 50 g) evoked neuronal responses of SNL rats. In contrast to carbamazepine, gabapentin also reduced evoked neuronal responses of sham-operated rats and there was no difference between the effects of gabapentin in SNL and sham-operated rats. Robust behavioural changes in the SNL model of neuropathy are paralleled by a temporal increase in spontaneous activity and a paradoxical decrease in evoked spinal neuronal responses. The peripheral nerve dysfunction reveals an effect of carbamazepine which is maintained throughout the observation period, validating this experimental approach. Gabapentin, a novel treatment for neuropathic pain states, also reduced neuronal responses, but the actions of the drug were not dependent on nerve injury. Further studies at the spinal level may shed light on the physiology and pharmacology of the aberrant processes associated with neuropathic pain.

Acetates↗

PubMed1998

UP 202-56, an adenosine analogue, selectively acts via A1 receptors to significantly decrease noxiously-evoked spinal c-Fos protein expression.

The effects of oral administration of UP 202-56, an adenosine analogue, were assessed on carrageenan-induced spinal c-Fos protein expression and peripheral oedema. Three hours after intraplantar injection of carrageenan (6 mg/150 microl of saline), in awake rats, numerous c-Fos-like immunoreactive (c-Fos-LI) neurons in the dorsal horn of L4-L5 lumbar segments of the spinal cord (191 +/- 8; 184 +/- 10; 205 +/- 7 c-Fos-LI neurons per 40 microm section, for carrageenan controls in three experimental series performed in this study, respectively) and an extensive peripheral oedema were observed. Oral UP 202-56 (10, 30 or 50 mg/kg) dose-dependently reduced the number of carrageenan-induced c-Fos-LI neurons (r = 0.931. P < 0.0001), with the highest dose of UP 202-56 producing 72 +/- 4% reduction of the total number of carrageenan-induced spinal c-Fos-LI neurons, and 12 +/- 3% and 33 +/- 6% of reduction of control carrageenan oedema at paw and ankle levels, respectively. DPCPX (1 mg/kg i.p.), a selective adenosine A1 receptor antagonist, which injected alone had no effect on carrageenan-induced spinal c-Fos expression and peripheral oedema, blocked the effects of UP 202-56 (30 mg/kg p.o.) on the number of carrageenan-induced c-Fos-LI neurons. In addition, DPCPX did not modify the effects of UP 202-56 on carrageenan-induced peripheral oedema. DMPX (1 mg/kg i.p.), a somewhat selective adenosine A2 receptor antagonist, which injected alone had no significant effect on carrageenan-induced spinal c-Fos protein expression and peripheral oedema, did not influence the effects of UP 202-56 (30 mg/kg p.o.) on both carrageenan-induced spinal c-Fos expression and peripheral oedema. Our results demonstrate that UP 202-56 dose-dependently reduced the spinal c-Fos protein expression in carrageenan model of inflammatory pain. The ability of DPCPX to block the effect of UP 202-56, in contrast to the lack of effect of DMPX, increased evidence for a predominant role of adenosine A1 receptors activation in the mechanism of action of UP 202-56. These results increase evidence for a role of adenosine in the modulation of nociceptive transmission and support the antinociceptive action of adenosine analogues, such as UP 202-56, in inflammatory pain processes.

Adenosine↗

PubMed1998

The mouse Mid1 gene: implications for the pathogenesis of Opitz syndrome and the evolution of the mammalian pseudoautosomal region.

We have recently reported isolation of the gene responsible for X-linked Opitz G/BBB syndrome, a defect of midline development. MID1 is located on the distal short arm of the human X chromosome (Xp22. 3) and encodes a novel member of the B box family of zinc finger proteins. We have now cloned the murine homolog of MID1 and performed preliminary expression studies during development. Mid1 expression in undifferentiated cells in the central nervous, gastrointestinal and urogenital systems suggests that abnormal cell proliferation may underlie the defect in midline development characteristic of Opitz syndrome. We have also found that Mid1 is located within the mouse pseudoautosomal region (PAR) in Mus musculus , while it seems to be X-specific in Mus spretus. Therefore, Mid1 is likely to be a recent acquisition of the M. musculus PAR. Genetic and FISH analyses also demonstrated a high frequency of unequal crossovers in the murine PAR, creating spontaneous deletion/duplication events involving Mid1. These data provide evidence for the first time that genetic instability of the PAR may affect functionally important genes. In addition, we show that MID1 is the first example of a gene subject to X-inactivation in man while escaping it in mouse. These data contribute to a better understanding of the molecular content and evolution of the rodent PAR.

Abnormalities, Multiple↗

PubMed1997

Inflammation reveals inhibition of noxious responses of rat spinal neurones by carbamazepine.

The effect of subcutaneously administered carbamazepine, a sodium channel blocker, on the electrically evoked C-fibre (noxious) vs A beta-fibre (innocuous) responses of dorsal horn neurones in non-inflamed and inflamed rats (3 h after plantar injection of carrageenan) was studied. Carbamazepine (0.5-5 mg/kg) significantly reduced the noxious evoked responses of the neurones under inflammatory, but not non-inflamed, conditions. The innocuous evoked responses of the neurones were not sensitive to carbamazepine under any conditions and administration of the vehicle alone did not influence any evoked response of these neurones. We propose that there are changes in the type, or proportion of, sodium channels underlying the transmission of noxious messages following peripheral inflammation which become sensitive to carbamazepine.

Analysis of Variance↗

PubMed1997

The contribution of peripheral bradykinin B2 receptors to carrageenan-evoked oedema and spinal c-Fos expression in rats.

Intraplantar co-injection of HOE140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a selective bradykinin B2 receptor antagonist (0.1, 1 and 10 micrograms), with carrageenan dose-dependently (r = 0.66, P < 0.01) reduced the carrageenan-evoked total number of c-Fos protein-like immunoreactive (c-Fos-LI) neurones (23 +/- 5%, 35 +/- 6% and 50 +/- 5% reduction; P < 0.01, P < 0.001 and P < 0.001, respectively). These reducing effects were dose-dependent for the number of c-Fos-LI neurones in both superficial (r = 0.70, P < 0.01) and deep (r = 0.53, P < 0.05) laminae. Intraplantar co-injection of HOE140 (0.1, 1 and 10 micrograms) with carrageenan significantly reduced the carrageenan-evoked paw (25 +/- 7%, 41 +/- 6% and 41 +/- 3% reduction; P < 0.001 for all) and ankle (46 +/- 6%, 61 +/- 5% and 61 +/- 5% reduction; P < 0.001 for all) oedema. Our results provide further evidence for the involvement of peripheral bradykinin B2 receptors in carrageenan-induced inflammatory nociceptive transmission.

Animals↗

PubMed1997

Distinct electrophysiological effects of two spinally administered membrane stabilising drugs, bupivacaine and lamotrigine.

A selective blockade of the relay of messages by C-fibres into the spinal cord is a logical approach to the reduction of nociceptive transmission. Here we compared the effect of two distinctly different sodium channel blockers, the local anaesthetic bupivacaine and the novel anti-epileptic lamotrigine, on the responses of dorsal horn neurones following noxious and innocuous stimulation. Dorsal horn neuronal responses following acute repetitive C-fibre electrical stimulation (three times the C-fibre threshold at 0.5 Hz) were recorded in intact halothane anaesthetised rats. Wind up, an enhanced C-fibre evoked response of dorsal horn neurones, and an associated post discharge were observed following repetitive stimulation. The effects of spinally administered bupivacaine and lamotrigine on the dorsal horn neuronal responses were investigated. Spinal bupivacaine (25-1000 microg/50 microl) dose dependently reduced the C-fibre evoked responses (r2 = 0.5, P < 0.0003), wind up (r2 = 0.4, P < 0.002) and the post discharge (r2 = 0.34, P < 0.005) of these neurones. The effects of bupivacaine were long lasting, up to 120 min post-administration. The Abeta-fibre evoked responses were not dose-dependently reduced by bupivacaine. Spinal lamotrigine (50-1000 microg/50 microl) did not significantly reduce the C- or Abeta-fibre evoked responses. In contrast there was a tendency for wind up and post discharge to be facilitated by lamotrigine. Although both bupivacaine and lamotrigine are sodium channel blockers, the effects of the two drugs on the C-fibre and Abeta-fibre evoked responses were completely different. Bupivacaine reduced C-fibre evoked responses whereas lamotrigine had a tendency to facilitate responses. The profile of sodium channel blockers would appear highly diverse and the status of lamotrigine as a potential analgesic remains unclear.

Anesthetics, Local↗

PubMed1997

The pharmacology of excitatory and inhibitory amino acid-mediated events in the transmission and modulation of pain in the spinal cord.

1. The aim of this review is to consider the relative roles of inhibitory and excitatory amino acid receptor-mediated events in the processes leading to pain transmission in the spinal cord. 2. Emphasis will be on the roles of the inhibitory and excitatory amino acids, GABA and glutamate, and how the relative balance between activity in these systems appears to determine the level of pain transmission. 3. The N-methyl-D-aspartate (NMDA) receptor for glutamate has been implicated in the generation and maintenance of central (spinal) states of hypersensitivity. It has been shown that activation of this receptor underlies wind-up, whereby the level of transmission of noxious messages is potentiated. Antagonists at this receptor-channel complex prevent or block enhanced (hyperalgesic) pain states induced by tissue damage, inflammation, nerve damage and ischemia. 4. Information concerning amplification systems in the spinal cord, such as the NMDA receptor, is a step toward understanding why and how a painful response is not always matched to the stimulus. Such events have parallels with other plastic events such as long-term potentiation (LTP) in the hippocampus. 5. However, the roles of inhibitory transmitter systems can also change insofar as opioid, adenosine and GABA transmission in the spinal cord can vary in different pain states. 6. Changes in GABA systems have been well-documented and discussion will center on whether this has clinical implications. 7. In addition to behavioral and electrophysiological approaches to the pharmacology of pain the current status of the use of markers of early onset genes such as c-fos, as monitors of activity, will be discussed. 8. Hyperalgesia would appear to be balanced by inhibitions during inflammatory conditions but not in neuropathic states, pains due to nerve damage. In the latter case, events reminiscent of LTP may predominate, whereas they are held in check by inhibitions under conditions of inflammation.

Animals↗