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Biomedical subjects

B A Meyerson

Publications and source records attributed to B A Meyerson.

At least 19 recordsLinked to original sources
PubMed2002

Endoscopic transthoracic sympathicotomy and peripheral microcirculation: effects of electric sympathetic chain stimulation, thermocoagulation and anaesthetic agents.

BACKGROUND: During endoscopic transthoracic sympathicotomy (ETS) in patients with hyperhidrosis it is useful to assess the effect of surgery peroperatively. However, the autonomic system is affected in various ways by different anesthetic agents. In the present study, the effect of ETS during either isoflurane or propofol anesthesia was evaluated by measuring changes in the finger pulp microcirculation using laser Doppler flowmetry (LDF). Electric stimulation of the sympathetic chain was used for identifying the sympathetic chain and to explore whether the anesthetic agents differentially influenced the LDF response to stimulation. METHODS: From a group of 12 patients with incapacitating palmar hyperhidrosis, six were randomly assigned to isoflurane and six to propofol anesthesia. LDF probes were attached to the ipsilateral finger pulp for continuous recording of peripheral blood flow during the ETS procedure. Electric stimulation (1 Hz, 10 Hz, and 100 Hz) was applied to the sympathetic paravertebral chain at the levels of the 2nd and 3rd sympathetic ganglia via a custom designed bipolar electrode. In eight of the patients LDF recordings were also performed in the awake state and compared with records obtained from eight healthy subjects. FINDINGS: In patients anesthetized with isoflurane, the base line finger pulp blood flow did not significantly differ from that of awake normal subjects, while those anesthetized with propofol had a lower base line flow, similar to that of awake subjects with hyperhidrosis. Stimulation of the sympathetic chain induced marked reduction of finger pulp microcirculation in both anesthetic groups, and this effect was frequency dependent during isoflurane anesthesia. After ETS a significant increase in flow was recorded only in the propofol group. Interpretation. The study demonstrates that the completeness of the sympathicotomy can only be peroperatively evaluated if an anesthetic agent with relatively low vasodilatory capacity, as e.g. propofol, is utilized.

Adult↗
PubMed2001

Neurosurgical approaches to pain treatment.

In a multidisciplinary approach to the management of chronic pain, neurosurgical methods are an indispensable part of the therapeutic armamentarium. With the exception of percutaneous interventions for trigeminal neuralgia and facet joint syndromes, most ablative pain surgery procedures (neurotomy, rhizotomy, sympathectomy, etc.) have been replaced by neuromodulatory approaches such as electrical stimulation of the central nervous system (CNS). However, cordotomy is still a valuable operation for certain forms of cancer related pains (Pancoast's syndrome, breakthrough pain) which are relatively resistant to pharmacotherapy. Another example of ablative surgery is the dorsal root entry zone (DREZ) operation, which is generally the only treatment option for pain due to root avulsion and segmental pain in spinal cord injury. Spinal cord stimulation (SCS) has proven to be most useful for the management of pain following peripheral nerve injury (including complex regional pain syndromes) and rhizopathy. For these conditions which are otherwise often therapy resistant, SCS may produce substantial and long-lasting pain relief in 60-70% of the patients. Considering that such pains are common and the fact that SCS has been shown to be cost-effective, this treatment is no doubt at present underused. Complications and side-effects are very rare. SCS has also been found to be useful for pain in peripheral vascular disorders and angina pectoris. In the latter condition the overall results are favorable in about 80% of patients with a significant reduction of the frequency and severity of angina attacks and the need for nitrates. Stimulation of the motor cortex is a novel and promising treatment of central, post-stroke pain and painful trigeminal neuropathy.

Cordotomy↗
PubMed2000

Mechanisms of spinal cord stimulation in neuropathic pain.

The understanding of the mode of action of spinal cord stimulation (SCS) as treatment of neuropathic pain is still fragmentary. SCS evolved from the gate-control theory postulating a spinal modulation of noxious inflow, but there is little evidence that SCS influences nociceptive pain; pain relief in peripheral vascular disease and angina pectoris is presumably secondary to other SCS effects. In man, SCS may effectively abolish both continuous and evoked pain (tactile/thermal allodynia) whereas induced, acute nociceptive pain is unaffected. Recent SCS studies performed on rat models of mononeuropathy have demonstrated a preferential effect on A beta fiber mediated functions, and the hyperexcitability of wide-dynamic-range dorsal horn neurons was attenuated. These effects were coupled to increased release of GABA and reduced glutamate and aspartate release in the dorsal horn. Intrathecal administration of GABA, baclofen and adenosine enhanced the SCS effect on tactile allodynia even in previously non-responsive rats. Preliminary results indicate that gabapentin may have a similar effect. GABAergic and adenosine-related mechanisms conceivably represent only examples of a number of putative receptor systems involved in SCS. Clinical trials have been initiated exploring the possibility to improve the efficacy of SCS by concomitant pharmacotherapy.

Animals↗
PubMed1999

Spinal cord stimulation attenuates dorsal horn neuronal hyperexcitability in a rat model of mononeuropathy.

The mechanisms underlying the relief of neuropathic pain of peripheral origin by spinal cord stimulation (SCS) are poorly understood. The present study was designed to investigate the effects of SCS on evoked and spontaneous discharges in dorsal horn neurons in intact and in nerve-injured rats subjected to partial sciatic nerve ligation according to Seltzer et al. (1990). Tactile sensitivity in the hind paw was assessed in behavioral tests using von Frey filaments. The presence of 'allodynia' was defined as a withdrawal response to a filament of 10 g or less. Under halothane/oxygen anesthesia the effects of SCS (50 Hz, 0.2 ms, 80-620 microA, 5 min.) on mechanically evoked (brush and innocuous press on the hind paw) responses and spontaneous discharges were investigated in wide-dynamic range (WDR) neurons in three groups of animals: (1) rats that displayed 'allodynia' after nerve ligation (2) rats without signs of 'allodynia' after surgery and (3) control, intact rats. A significantly increased frequency of spontaneous discharge and of responsiveness to brush and press was found in the group of allodynic, as compared with non-allodynic and control rats. The majority (63%) of the investigated neurons in these animals displayed afterdischarge in response to press stimulation. SCS induced a significant depression of both the principal response and the afterdischarge in allodynic rats: the discharge during brush stimulation was reduced to 86 +/- 8.2% and during press to 77.4 +/- 4.5% as compared with the prestimulation value. These depressive effects on evoked responses in allodynic rats outlasted SCS by 10.5 +/- 1.7 min during which time the responses gradually recovered. The frequency of spontaneous discharge was markedly decreased in approximately one third of the neurons, whereas in another third it was increased. In non-allodynic and control rats, SCS had no significant depressive effects on the evoked responses and spontaneous discharge. The results suggest that SCS may provide a suppressive action on dorsal horn neuronal hyperexcitability associated with signs of peripheral neuropathy. The suppressive effect of SCS on tactile allodynia, as previously observed in behavioral experiments, presumably corresponds to a normalization of the excitability of WDR cells in response to innocuous stimuli.

Animals↗
PubMed1999

Regulation of galanin and neuropeptide Y in dorsal root ganglia and dorsal horn in rat mononeuropathic models: possible relation to tactile hypersensitivity.

The expression of galanin and neuropeptide Y in rat lumbar 5 (L5) dorsal root ganglia and dorsal horn (L4-5) was studied after four types of peripheral nerve injury using immunohistochemistry and in situ hybridization. The possible correlation between these two peptides and tactile allodynia-like behaviour was analysed as well. The models employed were the Gazelius (photochemical lesion) and Seltzer and Bennett (constriction lesions) models, as well as complete sciatic nerve transection (axotomy). Two weeks after surgery, the Gazelius model rats more frequently displayed a greater tactile allodynia than the rats from the Seltzer and Bennett models. Tactile allodynia was not observed in any of the axotomized rats. A marked increase in the number of galanin-immunoreactive and galanin messenger RNA-positive neuron profiles was observed in ipsilateral dorsal root ganglia in all types of models. The increase in allodynic rats (Gazelius, Seltzer and Bennett models) was less pronounced than that after axotomy. In addition, in the Bennett model the number of galanin-immunoreactive neurons was significantly lower in allodynic rats as compared to non-allodynic rats, and the same tendency, but less obvious was found in the Seltzer model. Furthermore, an increase in galanin-immunoreactive fibres was found in the superficial laminae of the ipsilateral dorsal horn in all lesion models, especially in lamina II. A dramatic increase in the number of neuropeptide Y and neuropeptide Y messenger RNA-positive neuron profiles was also found in the ipsilateral dorsal root ganglia in all models, but no significant difference was found in peptide levels between allodynic and non-allodynic rats in any of the models. The present results suggest that the levels of endogenous galanin may play a role in whether or not allodynia develops in the Bennett model.

Animals↗
PubMed1999

Lesion topography and outcome after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder: relevance of the right hemisphere.

OBJECTIVES: Obsessive-compulsive disorder is a common mental disorder, notorious for its chronicity and intractability. Stereotactic lesions within the anterior limb of the internal capsule have been shown to provide symptomatic relief in such refractory cases, but only few systematic evaluations have correlated anatomic lesion location with individual postoperative outcome. PATIENTS AND METHODS: Between 1976 and 1989, extremely disabled and otherwise intractable patients with a chronic deteriorating clinical course of obsessive-compulsive disorder underwent bilateral thermocapsulotomy (n = 22) or radiosurgical gamma knife capsulotomy (n = 13) at the Karolinska Hospital, Stockholm. Clinical morbidity was monitored prospectively pre- and postoperatively by using standardized psychiatric rating scales. In 29 patients (thermocapsulotomy, n = 19; gamma knife capsulotomy, n = 10), both psychiatric and magnetic resonance imaging follow-up data (median, 8.4 yr) were available. RESULTS: A right-sided anatomically defined lesion volume was identified in all successfully treated patients. This common topographic denominator was defined in the approximate middle of the anterior limb of the internal capsule on the plane parallel to the anterior commissure-posterior commissure line at the level of the foramen of Monro and 4 mm above on the plane defined by the internal cerebral vein. This region was unaffected in patients with poor outcomes. On the left side, no particular lesion topography was associated with clinical outcome. Topographic differences of lesion overlap between good and poor outcome groups were significant for the right side (Fisher's exact test, P < 0.005). CONCLUSION: The current anatomic long-term analysis after thermocapsulotomy or gamma knife capsulotomy for obsessive-compulsive disorder reveals common topographic features within the right-sided anterior limb of the internal capsule independent of treatment modality.

Adult↗
PubMed1998

Effect of spinal cord stimulation on tactile hypersensitivity in mononeuropathic rats is potentiated by simultaneous GABA(B) and adenosine receptor activation.

In rats with abnormally low withdrawal thresholds ('allodynia') in one hindpaw induced by a photochemical sciatic lesion, an intrathecal catheter was inserted to the lumber enlargement and an epidural electrode was implanted at T11. I.t. administration of GABA(B) or adenosine A1 receptor agonists (baclofen, R(-)-N6-(2-phenylisopropyl)adenosine (R-PIA)) suppressed allodynia in a dose-dependent fashion. When the two agonists were given together, each in an ineffective dose, there was a normalization of the thresholds. Rats, in which spinal cord stimulation (SCS) could not suppress the allodynia (non-responders), were transformed into SCS-responders by injection of baclofen and R-PIA in low, ineffective doses, combined with SCS. In SCS responding rats, combination of a selective GABA(B) and an adenosine A1 receptor antagonist (CGP 55845, CPT) in low, ineffective doses abolished the SCS-induced threshold normalization. These results indicate that GABAergic and adenosine-dependent mechanisms are involved in the SCS effect and further suggest a strategy for enhancing the therapeutic efficacy of SCS.

Adenosine↗
PubMed1997

Adenosine receptor activation suppresses tactile hypersensitivity and potentiates spinal cord stimulation in mononeuropathic rats.

The aim of the present study was to investigate the intrathecal (i.t.) action of a selective A1-adenosine receptor agonist, R-phenylisopropyl adenosine (R-PIA), on tactile withdrawal thresholds in a rat model of mononeuropathy produced by sciatic chronic constriction injury (CCI). An additional aim was to examine whether adenosine receptor activation is involved in the effects of spinal cord stimulation (SCS), which activates low-threshold fibers and suppresses touch-evoked pain both in patients and in experimental animals with neuropathy. Animals presenting hindlimb withdrawal to von Frey filaments with a bending force of < 7.5 g on the lesioned side (compared to > or = 35 g in the normal limb), were considered as having tactile hypersensitivity ("allodynia'). R-PIA (1-10 nmol i.t.) induced a dose-dependent suppression of the tactile allodynia without producing impairment of motor function. The effect of R-PIA (3 nmol i.t.), a clearly submaximal dose, was abolished by concomitant treatment with the selective A1-adenosine receptor antagonist cyclopentylxanthine (10 nmol i.t.). In animals where SCS failed to influence tactile allodynia, concomitant i.t. administration of R-PIA (3 nmol) and SCS induced a clear-cut and long-lasting suppression of the hypersensitivity to tactile stimulation. In conclusion, adenosine receptor stimulation antagonizes tactile hypersensitivity in a CCI model of mononeuropathy and potentiates the action of spinal cord stimulation.

Animals↗
PubMed1997

Obsessive compulsive disorder and the right hemisphere: topographic analysis of lesions after anterior capsulotomy performed with thermocoagulation.

Considerable but uncontrolled evidence suggests that stereotactic capsulotomy by means of thermolesions may provide symptomatic relief for patients with otherwise therapy refractory "malignant" obsessive compulsive disorder (OCD). Unlike in other functional stereotactic interventions, target localization for capsulotomy is based upon anatomical definition only. Few systematic attempts have been made to correlate the site and size of the capsular lesions with postoperative clinical outcome. Between 1976 and 1989 bilateral thermo-capsulotomy (TC) was performed in 22 OCD patients. In 19 patients complete quantitative pre- and postoperative psychiatric rating of OCD symptoms and long-term postoperative MRI studies were available. Cohorts of patients fulfilling criteria for good or poor outcome were contrasted, cases with intermediate treatment effect being excluded. Median postoperative MRI follow-up was 8.4 years (2.4-20.3 y). 9/19 patients fulfilled criteria for good postoperative outcome. In these patients all lesion sites overlapped covering a small area within the right anterior limb of the internal capsule. Lesions within the group of patients with poor outcome (n = 5) were located elsewhere, mostly further anterior in the internal capsule. Differences of lesion overlap between the two outcome groups were significant for the right side (Fisher's Exact Test: p < 0.005). Common topographic features of lesion sites within the right internal capsule were identified in OCD patients responding favourably to capsulotomy.

Adult↗
PubMed1997

Spinal cord stimulation attenuates augmented dorsal horn release of excitatory amino acids in mononeuropathy via a GABAergic mechanism.

Neuropathic pain may be effectively relieved by electric stimulation of the spinal cord (SCS). However, the underlying mechanisms for the ensuing pain relief are poorly understood. In a rat model of neuropathy displaying hypersensitivity to innocuous tactile stimuli, (allodynia), we have earlier demonstrated that SCS may normalise withdrawal response thresholds. In the present study, using microdialysis, it is shown that SCS induces a decreased release of the dorsal horn excitatory amino acids (EAA), glutamate and aspartate, concomitant with an increase of the GABA release. Local perfusion with a GABA(B)-receptor antagonist in the dorsal horn transiently abolishes the SCS-induced suppression of the EAA release. Thus, the effect of SCS on neuropathic pain and allodynia may be due to an activation of local GABAergic mechanisms inhibiting the EAA release which is chronically elevated in such conditions.

Animals↗
PubMed1997

Incidence of mononeuropathy in rats is influenced by pre-emptive alteration of spinal excitability.

Both clinical and experimental data support the notion that the development of neuropathic pain is related to the state of excitability at the time of nerve injury. The present study was performed to investigate whether altering spinal excitability immediately before creation of a chronic constriction nerve injury in rats can influence the incidence of tactile hypersensitivity ('allodynia') by using pre-emptive: (1) intrathecal injection of a GABAB agonist or antagonists; (2) intrathecal lidocaine; or (3) C-fibre activation by electric stimulation. The incidence of tactile hypersensitivity was significantly reduced by the GABA(B) agonist baclofen while it was markedly enhanced by the administration of the GABA(B) antagonists 5-AVA and CGP 55845, as well as by C-fibre stimulation. Intrathecal administration of lidocaine did not influence the incidence of hypersensitivity. The results suggest that GABAergic mechanisms play an important role in the development of tactile hypersensitivity, and suggest that GABA(B) receptor agonists may be used as pre-emptive treatment to prevent the development of postinjury neuropathic pain.

Journal Article↗
PubMed1997

Modulation of spinal pain mechanisms by spinal cord stimulation and the potential role of adjuvant pharmacotherapy.

Experimental studies indicate that the effects of spinal cord stimulation (SCS) on 'hypersymptoms' in neuropathic pain conditions may at least partly be mediated via GABAergic and adenosine-dependent mechanisms. Concomitant intrathecal administration of receptor-active drugs modulating the function of the GABA and adenosine systems may both depress and enhance the effects of SCS. The first few patients with simultaneous intrathecal administration of the GABAB agonist baclofen and/or adenosine together with SCS, when the stimulation alone proved insufficient, are reported.

Adenosine↗
PubMed1996

Effects of spinal cord stimulation on touch-evoked allodynia involve GABAergic mechanisms. An experimental study in the mononeuropathic rat.

There is much evidence that tactile allodynia in rat models of mononeuropathy produced by sciatic nerve constriction is linked to disturbance of spinal GABAergic functions. Spinal cord stimulation (SCS) applied to such animals via chronically implanted electrodes may in some of the animals induce a significant increase of the withdrawal threshold in response to innocuous mechanical stimulation with von Frey filaments applied to the paw of the nerve ligated leg. The present study was performed in mononeuropathic animals with definite signs of tactile allodynia, which did not respond to SCS, GABA and the GABAB-agonist baclofen were administered intrathecally, in doses per se insufficient to influence the withdrawal thresholds, together with the previously ineffective SCS. This combination resulted in a marked and long-lasting increase of the thresholds. The GABAA-agonist muscimol given together with SCS also produced a similar, but less prominent threshold increase. The GABAB-antagonist 5-aminovaleric acid (5-AVA) produced a transient suppression of the threshold increase induced by SCS together with either GABA or baclofen. In contrast, the GABAA-antagonist bicuculline had no apparent inhibitory effect on the threshold augmentation produced by SCS combined with GABA or baclofen. It is concluded that SCS may operate by upgrading the spinal GABAergic systems and that its potential for producing pain relief is dependent upon the availability of responsive GABA-containing inhibitory interneurons. Moreover, it seems that the effects of SCS are more linked to the GABAB-than to the GABAA-receptor system.

Animals↗
PubMed1996

Daily spinal cord stimulation suppresses autotomy behavior in rats following peripheral deafferentation.

Autotomy in experimental animals following peripheral nerve section has been interpreted as a sign of pain corresponding to the chronic pain observed in patients with extensive nerve lesions. Such pain may be alleviated by spinal cord stimulation. In the present study, the effect of such stimulation, via chronically implanted electrodes, on autotomy behavior following sciatic nerve section was assessed in the rat. The stimulation was applied for 30 min daily during a 10-day period. There were four groups of animals, 16 in each, half of them females. Stimulating electrodes were implanted in all and one group served as control, receiving sham stimulation. In one group, the stimulation was started when autotomy was observed, one received stimulation from the day of nerve section, and in one it was begun three days before section. The onset of autotomy was significantly delayed in the latter two groups. When stimulation was applied as "treatment", autotomy ceased but reappeared after the 10-day stimulation period. The incidence and severity of autotomy was markedly delayed and reduced when the stimulation had been applied just after the nerve section or before. In the latter groups, the diminished degree of autotomy persisted for the entire observation period, lasting 60 days after the stimulation was stopped. It seems that spinal cord stimulation, albeit applied only once daily and during a limited time period, can protect the spinal cord from developing the state of hyperexcitability believed to be the major cause of autotomy behavior. Peripheral mechanisms may also play a role by the antidromic activity evoked by the stimulation in the sectioned peripheral nerve. This study shows that spinal cord stimulation, which is a commonly employed method for treating chronic neurogenic pain, may have long-lasting effects on plasticity changes in the spinal cord following peripheral nerve injury, even when the stimulation is applied for short periods of time.

Animals↗
PubMed1996

Release of gamma-aminobutyric acid in the dorsal horn and suppression of tactile allodynia by spinal cord stimulation in mononeuropathic rats.

OBJECTIVE: The aim of the present study is to monitor the extracellular gamma-aminobutyric acid (GABA) levels in the lumbar dorsal horn of allodynic rats, which respond to spinal cord stimulation (SCS) with a normalization of the tactile withdrawal threshold. In addition, we monitored the GABA levels in nonresponding and sham-stimulated rats. METHODS: Partial constriction injury of the sciatic nerve was performed, and a permanent electrode for SCS was inserted into the spinal canal. The response to SCS was assessed with von Frey hairs in awake animals. Later, microdialysis was performed in the dorsal horn of the spinal cord under halothane anesthesia. The concentration of GABA in the microdialysate was assessed by high-performance liquid chromatography. RESULTS: Extracellular GABA levels in rats with sciatic nerve lesions and allodynia (2.3 +/- 0.5 nmol/L) were significantly lower (P < 0.001) than in control rats with intact sciatic nerves (8.1 +/- 1.0 nmol/L), whereas only slightly decreased GABA levels (5.7 +/- 1.1 nmol/L) were detected in nonallodynic rats with sciatic nerve lesions. In the allodynic rats, which respond to SCS by a normalization of the tactile withdrawal threshold, significantly (P < 0.001) increased GABA levels (6.7 +/- 2.3 nmol/L) were detected after SCS. In contrast, neither the allodynic rats, which did not respond to SCS, nor the sham-stimulated allodynic rats displayed increased GABA levels in response to stimulation. CONCLUSION: Our results indicate that the development of allodynia, a common symptom in neuropathic pain states, may be linked to a decreased spinal release of GABA. We suggest that an SCS-induced release of GABA could be important for the suppression of allodynia observed in rats after SCS. Similar mechanisms could also be involved in the SCS-induced alleviation of pain in patients with peripheral neuropathy.

Animals↗