ASAP: A pharmacy-level intervention to increase nonprescription syringe sales to reduce bloodborne illnesses.

BACKGROUND: Pharmacy syringe sales are effective structural interventions to reduce bloodborne illnesses in populations, and are legal in all but two states. Yet evidence indicates reduced syringe sales in recent years. This study was designed as a feasibility test of an intervention to promote syringe sales by pharmacies in Arizona. METHODS: A four-month pilot among three Arizona pharmacies measured feasibility and acceptability through monthly surveys to 18 enrolled pharmacy staff members. RESULTS: Pharmacy staff reported increased ease of dispensing syringes across the study. Rankings of syringe dispensing as 'easiest' among 6 measured pharmacy practices increased from 38.9 % at baseline to 50.1 % post intervention module training, and to 83.3 % at pilot conclusion. The majority (72.2 %) of pharmacy staff agreed that intervention materials were easy to use. Over 70 % indicated that the intervention was influential in their "being more open to selling syringes without a prescription to someone who might use them for illicit drug use," and 61.1 % reported that in the future, they were highly likely to dispense syringes to customers who would use them to inject drugs. A vast majority (92 %) reported being likely to dispense subsidized naloxone if available to their pharmacy at no cost. CONCLUSIONS: An education-based intervention was found to be feasible and acceptable to pharmacy staff and had an observed impact on perceptions of ease and likelihood of dispensing syringes without a prescription to people who may use them to inject drugs.

Dialing for doctors: Secret shopper study of Arizona methadone and buprenorphine providers, 2022.

INTRODUCTION: Methadone and buprenorphine are effective and safe treatments for opioid use disorder (OUD) and also reduce overdose and all-cause mortality. Identifying and reaching providers of medication for opioid use disorder (MOUD) has proven difficult for prospective patients and researchers. OBJECTIVES: To assess the accuracy of government-maintained lists of Arizona (AZ) providers prescribing MOUD, and the extent to which these providers are accessible for treatment. METHODS: A two-phase study used a listing of 2376 AZ MOUD providers obtained from the U.S. Drug Enforcement Administration and the Substance Abuse and Mental Health Services Administration. Phase 1 assessed the accuracy of the listing using internet confirmatory research from May-October 2022. Phase 2 used the resulting list of 838 providers to assess provider availability, type of MOUD treatment provided, and accepted payment through secret shopper calls between November 16 and 30, 2022. RESULTS: Just over half (52.2 %, n = 1240) of providers were removed from the original listing during Phase 1. One quarter (25.9 %) were no longer in practice. Among the 833 eligible for the secret shopper Phase 2 study, 36.6 % (n = 307) were reached and identified as providing MOUD. A vast majority (88.1 %) of MOUD providers indicating treatment type were accepting new patients, however methadone was identified far more frequently than was likely permitted or provided for OUD. Providers were 5.5 times more likely to accept new patients if they accepted cash payment for services, and 4.9 times more likely if they accepted Medicaid. Rural areas remained underserved. CONCLUSIONS: The active population of MOUD providers is far smaller than surmised. DEA and SAMHSA provider listings are not sufficiently accurate for survey research sampling. Other means of representative sampling will need to be devised, and trusted lists of providers for prospective patients should be promoted, publicly available, and regularly maintained for accuracy. Providers that offer treatment should assure that public-facing staff have basic information about the practice, the treatment offered, and conditions for taking new patients. Concerted efforts must assure rural access at the most local levels to reduce patient travel burden.

Feasibility and acceptability of a proposed pharmacy-based harm reduction intervention to reduce opioid overdose, HIV and hepatitis C.

BACKGROUND: Evidence-based harm reduction intervention components which might benefit pharmacy patients have not been integrated and studied. OBJECTIVE: To investigate the feasibility and acceptability of a proposed pharmacy-based harm reduction intervention to reduce opioid overdose, HIV and hepatitis C called PharmNet. METHODS: Indiana managing pharmacists were surveyed in 2018 to assess the feasibility and acceptability of an intervention for opioid misuse screening, brief intervention, syringe and naloxone dispensing, and referrals provision. The Consolidated Framework for Implementation Research informed the survey development and analysis. RESULTS: The sample included 303 (30.8%) pharmacists; 215 (70.9%) provided detailed written comments. Intervention Characteristics: 83.3% believed PharmNet would benefit patients, and that staff could deliver the intervention with adequate training (70.0%). Inner Setting: While 77.2% believed their pharmacy culture supported practice change, 57.5% of chain pharmacists believed their pharmacies would not have time for PharmNet. Outer Setting: 73.3% believed additional addiction and overdose screening is needed in their community, and pharmacies should offer new services to help reduce opioid overdose and addiction among their patients (79.5%). A vast majority (97.7%) were asked by patients in the past 2 years about syringe related issues; 67.7% were asked about syringes for non-prescription injection drug use. Individuals Involved: While 62.4% believed PharmNet was within pharmacy scope of practice and 90.1% were comfortable consulting about syringe use, pharmacists reported that they had limited control over the implementation environment. PROCESS: 38.0% of pharmacists indicated interest in advising the development of PharmNet. CONCLUSIONS: An implementation trial of a modified version of PharmNet is likely feasible; yet will be challenged by structural pressures particularly in chain pharmacies. Successful implementation will involve the development of resources and policy components to manage outer and inner setting characteristics and align the intervention to the implementation environment.

Predicting Pharmacist Dispensing Practices and Comfort Related to Pre-exposure Prophylaxis for HIV Prevention (PrEP).

To identify factors associated with pharmacist dispensing practice and comfort counseling patients about pre-exposure prophylaxis for HIV prevention (PrEP). Cross-sectional 2016 census of Indiana managing pharmacists measured PrEP awareness, comfort dispensing and counseling patients. Modified Poisson models with robust error variance estimated relative risks and confidence intervals. 15.8% of 284 pharmacists had dispensed PrEP and 11.6% had consulted about it. Dispensing and comfort counseling were associated with confidence in knowledge about PrEP medication adherence and adverse effects of PrEP medication; awareness about PrEP before the survey, number of full time pharmacists in their pharmacy, and increases in new HIV cases from 2015 to 2016 in communities served. Comfort counseling about PrEP was associated with the belief that pharmacists can be an important resource for HIV and HCV treatment.

Predicting pharmacy naloxone stocking and dispensing following a statewide standing order, Indiana 2016.

BACKGROUND: While naloxone, the overdose reversal medication, has been available for decades, factors associated with its availability through pharmacies remain unclear. Studies suggest that policy and pharmacist beliefs may impact availability. Indiana passed a standing order law for naloxone in 2015 to increase access to naloxone. OBJECTIVE: To identify factors associated with community pharmacy naloxone stocking and dispensing following the enactment of a statewide naloxone standing order. METHODS: A 2016 cross-sectional census of Indiana community pharmacists was conducted following a naloxone standing order. Community, pharmacy, and pharmacist characteristics, and pharmacist attitudes about naloxone dispensing, access, and perceptions of the standing order were measured. Modified Poisson and binary logistic regression models attempted to predict naloxone stocking and dispensing, respectively. RESULTS: Over half (58.1%) of pharmacies stocked naloxone, yet 23.6% of pharmacists dispensed it. Most (72.5%) pharmacists believed the standing order would increase naloxone stocking, and 66.5% believed it would increase dispensing. Chain pharmacies were 3.2 times as likely to stock naloxone. Naloxone stocking was 1.6 times as likely in pharmacies with more than one full-time pharmacist. Pharmacies where pharmacists received naloxone continuing education in the past two years were 1.3 times as likely to stock naloxone. The attempted dispensing model yielded no improvement over the constant-only model. CONCLUSIONS: Pharmacies with larger capacity took advantage of the naloxone standing order. Predictors of pharmacist naloxone dispensing should continue to be explored to maximize naloxone access.

The role of the dorsolateral funiculi in the pain relieving effect of spinal cord stimulation: a study in a rat model of neuropathic pain.

Activation of the dorsal columns is relayed to supraspinal centers, involved in pain modulation, probably via the descending fibers in the dorsolateral funiculi (DLF). The present study examines the role of the DLF in the attenuation of pain-related signs by spinal cord stimulation (SCS). Several groups of rats were subjected to nerve injury and to chronic bilateral DLF lesions at C5-7 level. In each animal, two sets of miniature electrodes were implanted, a caudal system placed in the dorsal epidural space at low thoracic level and another implanted over the dorsal column nuclei, rostral to the lesions. Stimulation (50 Hz, 0.2 ms; 70 % of motor threshold) was applied for 5 min via either of the electrodes. Behavioral tests were used to assess the effects of SCS on the nerve injury-induced mechanical and cold hypersensitivity and heat hyperalgesia. Prior to application of SCS, antagonists to either of GABAA or B, 5-HT1 or 1-2 or α/ß-adrenergic receptors were injected i.p. Both stimulations produced comparable decreases (80-90 % of the control) of neuropathic manifestations in rats with intact spinal cords. DLF lesions attenuated the effects of both types of stimulation by about 50 %. Pretreatment with receptor antagonists differentially counteracted the effects of rostral and caudal stimulation; the inhibition with rostral stimulation generally being more prominently influenced. These results provide further support to the notion of important involvement of brainstem pain modulating centers in the effects of SCS. A major component of the inhibitory spinal-supraspinal-spinal loop is mediated by fibers running in the DLF.

Exploration of supraspinal mechanisms in effects of spinal cord stimulation: role of the locus coeruleus.

The neurobiological mechanisms of spinal cord stimulation (SCS) when applied for neuropathic pain are still incompletely known. Previous research indicates that brainstem circuitry is pivotal for the SCS effect. The present study aims at exploring the possible contribution to the SCS effects of the pain controlling system emanating from the locus coeruleus (LC) in the brain stem. Experiments were performed on the rat-spared nerve injury pain model. After evaluation of the attenuation of mechanical hypersensitivity induced by SCS, the effects of SCS on neuronal activity in the LC and on the noradrenaline (NA) content in the dorsal spinal cord were analyzed. SCS produced a significant increase in the discharge rate of LC neurons only in rats behaviorally responding to SCS as compared to non-responding and control animals. The NA content in the dorsal quadrant of the spinal cord ipsilateral to the nerve injury was analyzed using enzyme-linked immunosorbent assay in responding, non-responding and intact control rats both immediately following SCS and without SCS. No differences were found between these groups. In awake animals, lidocaine silencing of the ipsilateral LC or blocking of spinal noradrenergic system by intrathecal administration of α1,2 adrenoceptor antagonists failed to influence the antihypersensitivity effect of SCS. The present results indicate that the SCS-induced control of hypersensitivity in an experimental animal model of peripheral neuropathic pain may not be explained by the activation of direct spinal projections of noradrenergic LC neurons, while supraspinal projections of LC neurons still may play a role in the SCS effect.

The rostroventromedial medulla is engaged in the effects of spinal cord stimulation in a rodent model of neuropathic pain.

The neurobiological mechanisms underlying the suppression of neuropathic pain by spinal cord stimulation (SCS) are still incompletely known. The present study aims at exploring whether the descending pain control system in the rostroventromedial medulla (RVM) exerts a role in the attenuation of neuropathic pain by SCS. Experiments were performed in the rat spared nerve injury (SNI) pain model. The effects of SCS on neuronal activity of pronociceptive ON-like, antinociceptive OFF-like, and neutral cells, including 5-HT-like cells, in the RVM were analyzed in SCS responding and SCS non-responding SNI animals as well as in naïve controls. Decreased spontaneous activities in OFF-like cells and increased spontaneous activities in ON-like cells were observed in SNI animals, whereas the spontaneous activities of 5-HT-like and neutral cells were unchanged. SCS produced a prominent increase in the discharge of OFF- and 5-HT-like cells in SCS responding, but not in non-responding SNI animals or controls. Discharge rates of ON-like and neutral cell were not affected by SCS. In awake SNI animals, microinjection of a GABAA receptor agonist, muscimol, into the RVM significantly attenuated the antihypersensitivity effect induced by SCS while a non-selective opioid receptor antagonist, naltrexone, was ineffective. It is concluded that SCS may shift the reciprocal inhibitory and facilitatory pain modulation balance controlled by the RVM in favor of inhibition. This increase in the descending antinociceptive effect operates in concert with segmental spinal mechanisms in producing pain relief.

Spinal segmental and supraspinal mechanisms underlying the pain-relieving effects of spinal cord stimulation: an experimental study in a rat model of neuropathy.

Spinal cord stimulation (SCS) may alleviate certain forms of neuropathic pain; its mechanisms of action are, however, not fully understood. Previous studies have mainly been focused onto segmental spinal mechanisms, though there is evidence indicating a supraspinal involvement. This study aims to evaluate the relative importance of segmental and supraspinal mechanisms related to the activation of the dorsal columns (DCs). Rats were used to induce the spared nerve injury neuropathy and simultaneously subjected to chronic bilateral DC lesions at the C6-C8 level. Two pairs of miniature electrodes were implanted in each animal, with a monopolar system placed in the dorsal epidural space at a low thoracic level (below lesion) and a bipolar system placed onto the dorsal column nuclei (above lesion). Stimulation (50 Hz, 0.2 ms, 2-4V, 5 min) was applied via either type of electrodes, and tests for sensitivity to tactile and thermal stimuli were used to assess its inhibitory effects. Various receptor antagonists {bicuculline (GABA(A)), saclofen (GABA(B)), ketanserine (5HT(2)), methysergide (5HT(1-2)), phentolamine (α-adrenergic), propranolol (ß-adrenergic), sulpiride (D(2)/D(3) dopamine) or saline were injected prior to the SCS. Rostral and caudal stimulations produced a comparable inhibition of neuropathic manifestations, and these effects were attenuated by about 50% after DC lesions. Pretreatment with the various receptor antagonists differentially influenced the effects of rostral and caudal stimulation. Our findings suggest that both supraspinal and segmental mechanisms are activated by SCS, and that in this model with DC lesions, rostral and caudal stimulations may activate different synaptic circuitries and transmitter systems.

Inverse association of high-fat diet preference and anxiety-like behavior: a putative role for urocortin 2.

The aim of this study was to investigate whether the preference for a palatable high-fat diet (HFD) is associated with response to novelty and with anxiety-like behavior in rats and whether such fat preference correlates with gene expression of hypothalamic neuropeptides related to feeding. We subjected male rats to two tests of exploration of novel environments: the multivariate concentric square field (MCSF) and the elevated plus maze (EPM). The rats were then exposed to a 5-day test of preference for a palatable HFD versus reference diets. Messenger RNA (mRNA) levels of 21 neuropeptides were investigated by quantitative polymerase chain reaction. We found a strong positive correlation of HFD preference and open-arm activity in the EPM (% open-arm time, r(s) = 0.629, df = 26, P < 0.001). Thus, HFD preference was inversely associated with anxiety-like behavior. The same association was found for HFD preference and behavior in the MCSF (bridge entries, r(s) = 0.399, df = 23, P = 0.048). In addition, the HFD preference was positively correlated (r(s) = 0.433, df = 25, P = 0.021) with hypothalamic mRNA levels of urocortin 2 (Ucn 2). Moreover, behavior in the EPM was significantly correlated with expression levels of the receptor for Ucn 2, the corticotropin-releasing factor receptor 2, in the hypothalamus (r(s) = 0.382, df = 33, P = 0.022, pituitary (r(s) = 0.494, df = 31, P = 0.004) and amygdala (r(s) = 0.381, df = 30, P = 0.032). We conclude that preference for palatable HFD is inversely associated with anxiety and propose that Ucn 2 signaling may play a role in this association.

Assessing HIV care and unmet need: eight data bases and a bit of perseverance.

This study integrated healthcare information from multiple data sources to measure access to HIV primary care in the St. Louis, Missouri area between 1998-2002. We describe the process of creating the collective database and the degree to which each dataset contributed to the calculation of global variables such as evidence of HIV primary care. Descriptive analyses were used to measure evidence of HIV primary among the included data sources. This study was the first of its kind to study HIV primary healthcare access over a period of five years with integrated databases. Findings reinforce the importance of HIV laboratory values as indicators of access to HIV primary healthcare, particularly in the absence of other health data sets. Limitations to the study were posed by data availability and integration of data sources with varying purposes and sophistication.

Multicentre European study of thalamic stimulation for parkinsonian tremor: a 6 year follow-up.

AIM: To evaluate the results of ventral intermediate (Vim) thalamic deep brain stimulation (DBS) in patients with tremor predominant Parkinson's disease (PD) at 6 years post surgery. METHODS: This was a prolonged follow-up study of 38 patients from eight centres who participated in a multicentre study, the 1 year results of which have been published previously. Total scores as well as scores for individual items of the motor part and the disability part of the Unified Parkinson's Disease Rating Scale were used for evaluation. RESULTS: Tremor was still effectively controlled by DBS and appendicular rigidity and akinesia remained stable compared with baseline. Axial scores (speech, gait and postural instability), however, worsened, and in parallel the initial improvement in activities of daily living scores at the 1 year follow-up had disappeared at 6 years, despite sustained improvement of tremor. Remarkably, neither daily doses of dopaminergic medication nor fluctuations and dyskinesias had changed at 6 years compared with baseline in this particular patient group. CONCLUSION: This study confirms that patients with tremor dominant PD who do not present with fluctuations and dyskinesias may have a relatively benign progression of the disease. Vim DBS, although having no effect on akinesia and rigidity, is a relatively lenient surgical procedure and may still have a place for long term symptomatic control of PD tremor in selected patients.

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.

Chronic treatments with tacrine and (-)-nicotine induce different changes of nicotinic and muscarinic acetylcholine receptors in the brain of aged rat.

The present study evaluated effects of chronic treatment with tacrine and (-)-nicotine for 21 days on nicotinic and muscarinic acetylcholine receptors in the brains of old rats (24-25 months) by receptor autoradiography. The nicotinic receptor (nAChR) binding sites were measured by (-)-[3H]nicotine and [3H]epibatidine, and the muscarinic receptor (mAChR) binding sites by [3H]pirenzepine and [3H]AFDX 384. No change in (-)-[3H]nicotine binding was observed in all of the brain regions analysed following chroinic treatment with tacrine (10 mg/kg). Similarly, the [3H]epibatidine binding was not changed in most of the brain regions analysed except for a few brain regions where a decrease was observed in tacrine treated animals compared to control animals. Chronic treatment with (-)-nicotine (0.45 mg base/kg) significantly increased both (-)-[3H]nicotine and [3H]epibatidine bindings in every brain regions analysed except for the hippocampus when measured by (-)-[3H]nicotine. A significant decrease in [3H]AFDX 384 binding, but not in [3H]pirenzepine binding was observed in all of the brain regions analysed following the treatment with tacrine. These data suggest that chronic treatments with tacrine and (-)-nicotine differentially interfere and regulate the subtypes of nAChRs and mAChRs in the brain of aged rat. These data differ from what have been earlier observed in the brain of young adult rat following tacrine treatment, revealing some dynamic changes in receptor properties in the brain during aging.

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.

Androgen-linked control of carbonic anhydrase III expression occurs in rat perivenous hepatocytes; an immunocytochemical study.

Carbonic anhydrase (CA) isozymes CAII and CAIII were assayed by a radioimmunosorbent technique in liver cytosolic fractions and in isolated hepatocytes of adult male and female rats. Male livers contained 0.16 mg of CAII and 57 mg of CAIII per g cytosolic protein. Corresponding values for female livers were 0.34 mg CAII and 4 mg CAIII. Similar values and differences between CAII and III were found in isolated hepatocytes. Neonatal and adult castration of males reduced the CAIII levels to those of the females. Treatment with testosterone for three weeks restored the copulatory behaviour in the males castrated at adult age, but restored only partially the levels of CAIII. No significant effects of the endocrine manipulations were seen on CAII. Oophorectomy, with or without testosterone substitution, had no significant effect on CAII and CAIII levels in female rats. Immunohistochemistry and histochemistry showed that the regulation of CAIII is confined to perivenous hepatocytes. CAIII can therefore serve as a useful marker in the separation of these cells. CAIII appears to belong to the proteins and enzymes of the rat liver, known to be regulated via the hypothalamo-pituitary-liver axis. It may be used as a model of gene regulation in perivenous hepatocytes.

[Peripheral and central nervous system stimulation in chronic therapy-resistant pain. Background, hypothetical mechanisms and clinical experiences]. / Perifer och centralnervös stimulering vid kronisk terapiresistent smärta. Bakgrund, hypotetiska mekanismer och kliniska erfarenheter.

Severe neurogenic pain still constitutes a major problem since it is often resistant to conventional therapy. During the last 30 years electric activation of pain inhibitory mechanisms through stimulation both of peripheral nerves and of central nervous circuits has been used to great advantage. The simplest method of stimulation, transcutaneous electric nerve stimulation (TENS), is extensively used by physiotherapists as well as in pain clinics. The patient should always get his own stimulator for use at home. TENS originally served as a screening method to identify patients suitable for spinal cord stimulation therapy (SCS). The main indication is severe neuropathic pain of peripheral origin, but SCS has also been found valuable in extremity ischemia as well as in refractory angina pectoris. The most severe cases of neuropathic pain may benefit from intracranial stimulation via electrodes placed stereotactically in the posteromedial thalamus or epidurally over the motor cortex.

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.