The current state of training in pain medicine fellowships: An Association of Pain Program Directors (APPD) survey of program directors.

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME) approved the first pain medicine fellowship programs over three decades ago, designed around a pharmacological philosophy. Following that, there has been a rise in the transition of pain medicine education toward a multidisciplinary interventional model based on a tremendous surge of contemporaneous literature in these areas. This trend has created variability in clinical experience and education amongst accredited pain medicine programs with minimal literature evaluating the differences and commonalities in education and experience of different pain medicine fellowships through Program Director (PD) experiences. This study aims to gather insight from pain medicine fellowship program directors across the country to assess clinical and interventional training, providing valuable perspectives on the future of pain medicine education. METHODS: This study involved 56 PDs of ACGME-accredited pain fellowship programs in the United States. The recruitment process included three phases: advanced notification, invitation, and follow-up to maximize response rate. Participants completed a standard online questionnaire, covering various topics such as subcategory fields, online platforms for supplemental education, clinical experience, postgraduate practice success, and training adequacy. RESULTS: Surveys were completed by 39/56 (69%) standing members of the Association of Pain Program Directors (APPD). All PDs allowed fellows to participate in industry-related and professional society-related procedural workshops, with 59% encouraging these workshops. PDs emphasized the importance of integrity, professionalism, and diligence for long-term success. Fifty-four percent of PDs expressed the need for extension of fellowship training to avoid supplemental education by industry or pain/spine societies. CONCLUSION: This study highlights the challenge of providing adequate training in all Pain Medicine subtopics within a 12-month pain medicine fellowship. PDs suggest the need for additional training for fellows and discuss the importance of curriculum standardization.

Approaches to neuropathic amputation-related pain: narrative review of surgical, interventional, and medical treatments.

BACKGROUND/IMPORTANCE: Neuropathic amputation-related pain can consist of phantom limb pain (PLP), residual limb pain (RLP), or a combination of both pathologies. Estimated of lifetime prevalence of pain and after amputation ranges between 8% and 72%. OBJECTIVE: This narrative review aims to summarize the surgical and non-surgical treatment options for amputation-related neuropathic pain to aid in developing optimized multidisciplinary and multimodal treatment plans that leverage multidisciplinary care. EVIDENCE REVIEW: A search of the English literature using the following keywords was performed: PLP, amputation pain, RLP. Abstract and full-text articles were evaluated for surgical treatments, medical management, regional anesthesia, peripheral block, neuromodulation, spinal cord stimulation, dorsal root ganglia, and peripheral nerve stimulation. FINDINGS: The evidence supporting most if not all interventions for PLP are inconclusive and lack high certainty. Targeted muscle reinnervation and regional peripheral nerve interface are the leading surgical treatment options for reducing neuroma formation and reducing PLP. Non-surgical options include pharmaceutical therapy, regional interventional techniques and behavioral therapies that can benefit certain patients. There is a growing evidence that neuromodulation at the spinal cord or the dorsal root ganglia and/or peripheral nerves can be an adjuvant therapy for PLP. CONCLUSIONS: Multimodal approaches combining pharmacotherapy, surgery and invasive neuromodulation procedures would appear to be the most promising strategy for preventive and treating PLP and RLP. Future efforts should focus on cross-disciplinary education to increase awareness of treatment options exploring best practices for preventing pain at the time of amputation and enhancing treatment of chronic postamputation pain.

Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation: A Proposal for Standardization in Fellowship and Training Programs.

The need to be competent in neuromodulation is and should be a prerequisite prior to completing a fellowship in interventional pain medicine. Unfortunately, many programs lack acceptable candidates for these advanced therapies, and fellows may not receive adequate exposure to neuromodulation procedures. The American Society of Pain and Neuroscience (ASPN) desires to create a consensus of experts to set a minimum standard of competence for neurostimulation procedures, including spinal cord stimulation (SCS), dorsal root ganglion stimulation (DRG-S), and peripheral nerve stimulation (PNS). The executive board of ASPN accepted nominations for colleagues with excellence in the subject matter of neuromodulation and physician education. This diverse group used peer-reviewed literature and, based on grading of evidence and expert opinion, developed critical consensus guides for training that all accredited fellowship programs should adopt. For each consensus point, transparency and recusal were used to eliminate bias, and an author was nominated for evidence grading oversight and bias control. Pain Education and Knowledge (PEAK) Consensus Guidelines for Neuromodulation sets a standard for neuromodulation training in pain fellowship training programs. The consensus panel has determined several recommendations to improve care in the United States for patients undergoing neuromodulation. As neuromodulation training in the United States has evolved dramatically, these therapies have become ubiquitous in pain medicine. Unfortunately, fellowship programs and the Accreditation Council for Graduate Medical Education (ACGME) pain program requirements have not progressed training to match the demands of modern advancements. PEAK sets a new standard for fellowship training and presents thirteen practice areas vital for physician competence in neuromodulation.

Efficacy and Safety of Cervical and High-Thoracic Dorsal Root Ganglion Stimulation Therapy for Complex Regional Pain Syndrome of the Upper Extremities.

OBJECTIVES: The purpose of this study was to evaluate analgesic and safety considerations for high thoracic and cervical dorsal root ganglion (DRG) neuromodulation for complex regional pain syndrome (CRPS). We hypothesized that DRG neuromodulation would provide sustained analgesia with complications like that of low thoracic or lumbar electrode implantation. MATERIALS AND METHODS: A single-center, retrospective study was conducted of patients with CRPS I or II of the upper extremities, refractory to previous therapies, who were treated with DRG neuromodulation in the upper thoracic and cervical spine. The primary outcome was successful DRG therapy, defined as ≥ 50% pain relief on a Numeric Rating Scale (NRS) 0 to 10 pain scale at six months after implantation. A secondary outcome was a reduction in daily opioid use after DRG therapy. RESULTS: After a DRG stimulation trial, 17 of 20 patients (85%) had ≥ 50% improvement in NRS pain and underwent a permanent pulse generator implant, with 100% endorsing ≥ 50% pain relief at six months. Mean NRS pain scores before DRG neuromodulation were 9.3 ± 1.1, with a mean reduction of 5.5 (95% CI, 4.5-6.6; p < 0.001) at six months. Ten patients were taking opioids at baseline; the median (interquartile range) dose was 45 mg (23 to 120) morphine equivalents (MME), which was reduced to 20 MME (15 to 40) at six months. The median reduction in daily MME use was -25 (95% CI, -100 to 20; p = 0.099). Six of 20 patients (30%) experienced a complication: three had lead migration; two experienced paresthesias; and one had a reduction in shoulder mobility. One patient had symptoms of a reversible spinal cord compression immediately after implant, requiring emergent electrode removal. CONCLUSIONS: DRG neuromodulation for patients with CRPS of the upper extremities produced clinically important analgesia and reduced opioid use for ≥ six months but was associated with one serious complication.

Six Month Interim Outcomes from SECURE: A Single arm, Multicenter, Prospective, Clinical Study on a Novel Minimally Invasive Posterior Sacroiliac Fusion Device.

INTRODUCTION: Sacroiliac joint disease is a prominent diagnosis across the world. A novel fixation technique employing a posterior approach, single point, bone allograft transfixation has proven to be helpful anecdotally. The purpose of this is study is to investigate prospectively the safety and efficacy of this approach. METHODS: A multicenter, prospective, single arm study was performed after patient identification and treatment with the novel posterior fusion, single-point transfixation system and followed for 24 months. Target enrollment is 100 patients. Interim results on the first 69 consecutive patients at 6 months is presented. Primary endpoint at 6-month analysis was Pain Intensity reduction by visual analogue scale and functional improvement by Oswestry Disability Index. Adverse events were assessed for safety analysis. RESULTS: In total, 69 patients were identified for this analysis. At 6 months, a mean improvement of 34.9 was identified by a reduction in VAS and functional improvement was demonstrated by a mean reduction in ODI of 17.7. There were three adverse events, all unrelated to the device. CONCLUSION: The posterior single point transfixation is safe and efficacious for the treatment of sacroiliac joint dysfunction with statistical improvements in pain and function.

The Neurostimulation Appropriateness Consensus Committee (NACC): Recommendations for Surgical Technique for Spinal Cord Stimulation.

INTRODUCTION: The field of neurostimulation for the treatment of chronic pain is a rapidly developing area of medicine. Although neurostimulation therapies have advanced significantly as a result of technologic improvements, surgical planning, device placement, and postoperative care are of equal importance to optimize outcomes. This Neurostimulation Appropriateness Consensus Committee (NACC) project intends to provide evidence-based guidance for these often-overlooked areas of neurostimulation practice. MATERIALS AND METHODS: Authors were chosen based on their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches of MEDLINE, BioMed Central, Current Contents Connect, Embase, International Pharmaceutical Abstracts, Web of Science, Google Scholar, and PubMed from the last NACC publication in 2017 to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations are based on evidence strength and consensus when evidence was scant. RESULTS: This NACC project provides guidance on preoperative assessment, intraoperative techniques, and postoperative management in the form of consensus points with supportive evidence. These results are based on grade of evidence, strength of consensus, and expert opinion. CONCLUSIONS: The NACC has given guidance for a surgical plan that encompasses the patient journey from the planning stage through the surgical experience and postoperative care. The overall recommendations are designed to improve efficacy and the safety of patients undergoing these neuromodulation procedures and are intended to apply throughout the international community.

The Neuromodulation Appropriateness Consensus Committee on Best Practices for Dorsal Root Ganglion Stimulation.

INTRODUCTION: The Neuromodulation Appropriateness Consensus Committee (NACC) is dedicated to improving the safety and efficacy of neuromodulation and thus improving the lives of patients undergoing neuromodulation therapies. With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion (DRG) stimulation has significantly improved the treatment of complex regional pain syndrome (CRPS), among other conditions. Through funding and organizational leadership by the International Neuromodulation Society (INS), the NACC reconvened to develop the best practices consensus document for the selection, implantation and use of DRG stimulation for the treatment of chronic pain syndromes. METHODS: The NACC performed a comprehensive literature search of articles about DRG published from 1995 through June, 2017. A total of 2538 article abstracts were then reviewed, and selected articles graded for strength of evidence based on scoring criteria established by the US Preventive Services Task Force. Graded evidence was considered along with clinical experience to create the best practices consensus and recommendations. RESULTS: The NACC achieved consensus based on peer-reviewed literature and experience to create consensus points to improve patient selection, guide surgical methods, improve post-operative care, and make recommendations for management of patients treated with DRG stimulation. CONCLUSION: The NACC recommendations are intended to improve patient care in the use of this evolving therapy for chronic pain. Clinicians who choose to follow these recommendations may improve outcomes.

The MIST Guidelines: The Lumbar Spinal Stenosis Consensus Group Guidelines for Minimally Invasive Spine Treatment.

BACKGROUND: Lumbar spinal stenosis (LSS) can lead to compression of neural elements and manifest as low back and leg pain. LSS has traditionally been treated with a variety of conservative (pain medications, physical therapy, epidural spinal injections) and invasive (surgical decompression) options. Recently, several minimally invasive procedures have expanded the treatment options. METHODS: The Lumbar Spinal Stenosis Consensus Group convened to evaluate the peer-reviewed literature as the basis for making minimally invasive spine treatment (MIST) recommendations. Eleven consensus points were clearly defined with evidence strength, recommendation grade, and consensus level using U.S. Preventive Services Task Force criteria. The Consensus Group also created a treatment algorithm. Literature searches yielded 9 studies (2 randomized controlled trials [RCTs]; 7 observational studies, 4 prospective and 3 retrospective) of minimally invasive spine treatments, and 1 RCT for spacers. RESULTS: The LSS treatment choice is dependent on the degree of stenosis; spinal or anatomic level; architecture of the stenosis; severity of the symptoms; failed, past, less invasive treatments; previous fusions or other open surgical approaches; and patient comorbidities. There is Level I evidence for percutaneous image-guided lumbar decompression as superior to lumbar epidural steroid injection, and 1 RCT supported spacer use in a noninferiority study comparing 2 spacer products currently available. CONCLUSIONS: MISTs should be used in a judicious and algorithmic fashion to treat LSS, based on the evidence of efficacy and safety in the peer-reviewed literature. The MIST Consensus Group recommend that these procedures be used in a multimodal fashion as part of an evidence-based decision algorithm.

Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists.

BACKGROUND: Over the past 2 decades, the use of intravenous ketamine infusions as a treatment for chronic pain has increased dramatically, with wide variation in patient selection, dosing, and monitoring. This has led to a chorus of calls from various sources for the development of consensus guidelines. METHODS: In November 2016, the charge for developing consensus guidelines was approved by the boards of directors of the American Society of Regional Anesthesia and Pain Medicine and, shortly thereafter, the American Academy of Pain Medicine. In late 2017, the completed document was sent to the American Society of Anesthesiologists' Committees on Pain Medicine and Standards and Practice Parameters, after which additional modifications were made. Panel members were selected by the committee chair and both boards of directors based on their expertise in evaluating clinical trials, past research experience, and clinical experience in developing protocols and treating patients with ketamine. Questions were developed and refined by the committee, and the groups responsible for addressing each question consisted of modules composed of 3 to 5 panel members in addition to the committee chair. Once a preliminary consensus was achieved, sections were sent to the entire panel, and further revisions were made. In addition to consensus guidelines, a comprehensive narrative review was performed, which formed part of the basis for guidelines. RESULTS: Guidelines were prepared for the following areas: indications; contraindications; whether there was evidence for a dose-response relationship, or a minimum or therapeutic dose range; whether oral ketamine or another N-methyl-D-aspartate receptor antagonist was a reasonable treatment option as a follow-up to infusions; preinfusion testing requirements; settings and personnel necessary to administer and monitor treatment; the use of preemptive and rescue medications to address adverse effects; and what constitutes a positive treatment response. The group was able to reach consensus on all questions. CONCLUSIONS: Evidence supports the use of ketamine for chronic pain, but the level of evidence varies by condition and dose range. Most studies evaluating the efficacy of ketamine were small and uncontrolled and were either unblinded or ineffectively blinded. Adverse effects were few and the rate of serious adverse effects was similar to placebo in most studies, with higher dosages and more frequent infusions associated with greater risks. Larger studies, evaluating a wider variety of conditions, are needed to better quantify efficacy, improve patient selection, refine the therapeutic dose range, determine the effectiveness of nonintravenous ketamine alternatives, and develop a greater understanding of the long-term risks of repeated treatments.

The parturient with implanted spinal cord stimulator: management and review of the literature.

Spinal cord stimulation (SCS) is an approved treatment for complex regional pain syndrome and other chronic pain conditions. These devices enable women with chronic pain to maintain relatively normal lives, with some encountering pregnancy. Use of previously implanted SCS systems in pregnant women is considered controversial due to lack of long-term prospective studies evaluating both maternal and fetal safety. Seven patients at a university pain clinic were identified as having SCS implanted before becoming pregnant. Data on these patients before, during, and after labor were collected through chart review and patient interview. Onset of labor varied among the 7 patients (2 preterm and 5 term). Mode of anesthesia for delivery included 4 neuraxial anesthetics, with 3 successfully obtaining an adequate level of anesthesia for delivery. Four general anesthetics were administered for cesarean delivery, one of which included a failed attempt at neuraxial anesthesia. All infants were born healthy. Management approaches and outcomes in our patients, as well as those previously reported are discussed within this article. Definitive conclusions cannot be drawn from this small cohort. We believe that management of a parturient with an implanted SCS requires careful planning between all peripartum physicians.

Evidence-based interventional pain medicine according to clinical diagnoses. 16. Complex regional pain syndrome.

Complex regional pain syndrome (CRPS), formerly known as reflex sympathetic dystrophy is a pain syndrome with an unclear pathophysiology and unpredictable clinical course. The disease is often therapy resistant, the natural course not always favorable. The diagnosis of CRPS is based on signs and symptoms derived from medical history and physical examination. Pharmacological pain management and physical rehabilitation of limb function are the main pillars of therapy and should be started as early as possible. If, however, there is no improvement of limb function and persistent severe pain, interventional pain management techniques may be considered. Intravenous regional blocks with guanethidine did not prove superior to placebo but frequent side effects occurred.Therefore this technique receives a negative recommendation (2 A-). Sympathetic block is the interventional treatment of first choice and has a 2 B+ rating. Ganglion stellatum (stellate ganglion) block with repeated local anesthetic injections or by radiofrequency denervation after positive diagnostic block is documented in prospective and retrospective trials in patients suffering from upper limb CRPS. Lumbar sympathetic blocks can be performed with repeated local anesthetic injections. For a more prolonged lumbar sympathetic block radiofrequency treatment is preferred over phenol neurolysis because effects are comparable whereas the risk for side effects is lower (2 B+). For patients suffering from CRPS refractory to conventional treatment and sympathetic blocks, plexus brachialis block or continuous epidural infusion analgesia coupled with exercise therapy may be tried (2 C+). Spinal cord stimulation is recommended if other treatments fail to improve pain and dysfunction (2 B+). Alternatively peripheral nerve stimulation can be considered, preferentially in study conditions (2 C+).

Response of chronic pain patients to terrorism: the role of underlying depression.

OBJECTIVES: This study seeks to identify characteristics of the chronic pain patient population that may increase vulnerability to vicariously experienced psychological trauma. DESIGN: Characteristics, including demographics and psychological measures, were evaluated by modeling change in visit rates to a university pain center immediately after the terrorist attacks of September 11, 2001. SETTING: University pain center. PATIENTS: A total of 570 patients with chronic pain. OUTCOME MEASURES: Visit rates, psychologists evaluation of depression, Beck Depression Inventory. RESULTS: Evaluation of psychological measures showed that depression was the most effective predictor of the postattack visit rate increase in chronic pain patients. The visit rate for nondepressed patients did not change significantly after the attacks, but approximately doubled for depressed patients. A more detailed analysis, performed by categorizing patients into one of four levels of depression, found that patients classified as "Mild to Moderately" depressed were most likely to show an increase in visits after the attacks. CONCLUSIONS: Chronic pain patients represent a vulnerable population, and the current study posits the possibility of predicting the most vulnerable individuals within that population. With information commonly contained in medical records, target populations may be identified for potential psychological trauma intervention to reduce the sequelae of vicariously experienced psychological trauma.

Cerebrospinal fluid and plasma pharmacokinetics of the cyclooxygenase 2 inhibitor rofecoxib in humans: single and multiple oral drug administration.

Cerebrospinal fluid (CSF) pharmacokinetics of orally administered cyclooxygenase 2 inhibitors, with single or multiple dosing, is of clinical relevance because it may relate to the analgesic efficacy of these drugs. We enrolled 9 subjects with implanted intrathecal catheters in the study. After 50-mg oral rofecoxib administration, the CSF drug concentration lagged slightly behind the plasma drug concentration. The ratio of the 24-h area under the drug-concentration curve (AUC) in CSF to plasma was 0.142. After daily dosing of rofecoxib 50 mg/d for 9 days, rofecoxib concentrations in plasma and CSF were larger on Day 9 than on Day 1, with the 24-h AUC on Day 9 more than twice the Day 1 AUC for both plasma and CSF. After nine consecutive daily doses of rofecoxib, the AUC(CSF)/AUC(plasma) ratio was 0.159. The important findings of this study are that CSF rofecoxib levels are approximately 15% of plasma levels and that repeated daily dosing more than doubles the AUC in CSF.

Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial.

CONTEXT: Controlling postoperative pain after knee replacement while reducing opioid-induced adverse effects and improving outcomes remains an important challenge. OBJECTIVE: To assess the effect of combined preoperative and postoperative administration of a selective inhibitor of cyclooxygenase 2 on opioid consumption and outcomes after total knee arthroplasty (TKA). DESIGN, SETTING, AND PATIENTS: Randomized, placebo-controlled, double-blind trial conducted June 2001 through September 2002, enrolling 70 patients aged 40 to 77 years and undergoing TKA at a university hospital in the United States. INTERVENTIONS: Patients were randomly assigned to receive 50 mg of oral rofecoxib at 24 hours and at 1 to 2 hours before TKA, 50 mg daily for 5 days postoperatively, and 25 mg daily for another 8 days, or matching placebo at the same times. MAIN OUTCOME MEASURES: Postoperative outcomes including postsurgical analgesic consumption and pain scores achieved, nausea and vomiting, joint range of motion, sleep disturbance, patient satisfaction with analgesia, and hematologic and coagulation parameters. RESULTS: Total epidural analgesic consumption and in-hospital opioid consumption were less in the group receiving rofecoxib compared with the group receiving placebo (P<.05). Median pain score (visual analog scale [VAS], 0-10) achieved for the knee was lower in the rofecoxib group compared with the placebo group during hospital stay (2.2 [interquartile range [IQR], 1.4-3.2] vs 3.5 [IQR, 2.7-4.3], P<.001) and 1 week after discharge (2.6 [IQR, 1.4-3.5] vs 3.7 [IQR, 2.9-4.7], P =.03). There was less postoperative vomiting in the rofecoxib group (6%) compared with the placebo group (26%) (P =.047), as well as a decrease in sleep disturbance compared with the placebo group on the night of surgery (P =.006) and on the first (P =.047) and second (P<.001) days postoperatively. Knee flexion was increased in the rofecoxib group compared with the placebo group at discharge (active flexion: mean [SD], 84.2 degrees [11.1 degrees ] vs 73.2 degrees [13.6 degrees ], P =.03; passive flexion: 90.5 degrees [6.8 degrees ] vs 81.8 degrees [13.4 degrees ], P =.05) and at 1 month postoperatively (109.3 degrees [8.5 degrees ] vs 100.8 degrees [11.8 degrees ], P =.01), with shorter time in physical therapy to achieve effective joint range of motion. The rofecoxib group was more satisfied with analgesia and anesthesia at discharge compared with the placebo group (median satisfaction score, 4.3 [IQR, 3.0-4.7] vs 3.3 [IQR, 2.3-4.3], respectively; P =.03), and the differences persisted at 2-week and at 1-month follow-up. There was no intergroup difference in surgical blood loss (P>.05 for both intraoperative and postoperative blood loss). CONCLUSION: Perioperative use of an inhibitor of cyclooxygenase 2 is an effective component of multimodal analgesia that reduces opioid consumption, pain, vomiting, and sleep disturbance, with improved knee range of motion after TKA.

An updated interdisciplinary clinical pathway for CRPS: report of an expert panel.

The goal of treatment in patients with complex regional pain syndrome (CRPS) is to improve function, relieve pain, and achieve remission. Current guidelines recommend interdisciplinary management, emphasizing 3 core treatment elements: pain management, rehabilitation, and psychological therapy. Although the best therapeutic regimen or the ideal progression through these modalities has not yet been established, increasing evidence suggests that some cases are refractory to conservative measures and require flexible application of the various treatments as well as earlier consideration of interventions such as spinal cord stimulation (SCS). While existing treatment guidelines have attempted to address the comprehensive management of CRPS, all fail to provide guidance for contingent management in response to a sudden change in the patient's medical status. This paper reviews the current pathophysiology as it is known, reviews the purported treatments, and provides a modified clinical pathway (guideline) that attempts to expand the scope of previous guidelines.

Psychological differences between reflex sympathetic dystrophy and non-RSD chronic pain patients.

This study examined possible psychological differences between Reflex Sympathetic Dystrophy (RSD) and non-RSD chronic pain patients. Unlike the few previous studies in this area, this study controlled statistically for age and pain duration differences across diagnostic groups, and included a non-RSD limb pain control group. Subjects were a consecutive series of 34 RSD, 50 non-RSD limb pain (Limb), and 165 low back pain (LBP) patients presenting for treatment at the Rush Pain Center. Analyses revealed that RSD patients reported more somatization and phobic anxiety on the Brief Symptom Inventory than LBP patients. RSD patients also reported greater coping with pain through diverting attention than LBP patients did on the Coping Strategies Questionnaire. Comparisons between the RSD and Limb groups revealed no significant differences with the exception of somatization scores. The relationship between distress and pain severity was found to be stronger in RSD and Limb patients than in LBP patients. These results provide partial support for clinical assumptions that RSD patients are more psychologically dysfunctional than other chronic pain patients. However, these conclusions do not generalize across all comparison groups. The fact that RSD and non-RSD limb pain patients were quite similar on nearly all measures suggests that sympathetic mediation of pain is not the source of these psychological differences.

Effect of intrathecal tizanidine on antinociception and blood pressure in the rat.

Experiments were performed in rats to determine if the alpha 2-adrenergic agonist tizanidine has an antinociceptive effect when injected intrathecally, and whether the analgesia is accompanied by changes in blood pressure. Rats were chronically implanted with catheters in the lumbar subarachnoid space. Antinociception was evaluated in conscious rats with the tail-flick test. Increasing tizanidine doses produced increases in analgesic efficacy, with 25 micrograms producing a significant long-lasting antinociception. This tail-flick analgesia was very similar to that produced by clonidine (25 micrograms) and morphine (8 micrograms) in peak effect and duration. Doses as high as 250 micrograms produced only a transient hind limb motor dysfunction in 43% of the animals. Daily injections of 25 micrograms tizanidine over 5 days produced a decrease in antinociception, with the peak effect at day 5 at 59% of that at day 1. Blood pressure, in rats lightly anesthetized with halothane, was not affected by tizanidine injections up to 250 micrograms. Tizanidine appears to be a promising non-opiate analgesic for intrathecal usage.