Pain Control Associated With Gabapentinoid Prescription After Elective Total Knee Arthroplasty.

BACKGROUND: Gabapentinoid (GABA) prescribing has substantially increased as a nonopioid analgesics for surgical conditions. We examined the effectiveness of GABA use for postoperative pain control among patients receiving total knee arthroplasty (TKA). METHODS: This retrospective cohort study using 2016 to 2019 data from a 20% national sample of Medicare enrollees included patients aged 66 and over years who received an elective TKA, were discharged to home, received home health care, and had both admission and discharge assessments of pain (n = 35,186). Study outcomes were pain score difference between admission and discharge and less-than-daily pain interfering with activity at discharge. Opioid and GABA prescriptions after surgery and receipt of nerve block within 3 days of surgery were also assessed. RESULTS: There were 30% of patients who had a pain score decrease of 3 to 4 levels and 55.8% had pain score decreases of 1 to 2 levels. In multivariable analyses, receiving a nerve block was significantly associated with pain score reduction. A GABA prescription increased the magnitude of pain score reduction among those receiving a nerve block. Results from inverse probability weighted analysis with propensity score showed that coprescribing of GABA and low-dose opioid was associated with significantly lower pain scores. CONCLUSIONS: Post-TKA opioid use was not associated with pain score reduction. Receiving a nerve block was associated with a modest pain score reduction. Co-prescribing GABA with low-dose opioid or receiving a nerve block was associated with increasing magnitudes of pain reduction. Further research should identify alternatives to opioid use for managing postoperative TKA pain.

SLN124, a GalNAc conjugated 19-mer siRNA targeting tmprss6, reduces plasma iron and increases hepcidin levels of healthy volunteers.

SLN124, an N-acetylgalactosamine conjugated 19-mer short interfering RNA, is being developed to treat iron-loading anemias (including beta-thalassemia and myelodysplastic syndromes) and myeloproliferative neoplasms (polycythemia vera). Through hepatic targeting and silencing of the TMPRSS6 gene, SLN124 increases endogenous hepcidin synthesis. This is the first clinical report of an siRNA targeting a component of iron homeostasis. This first-in-human, phase 1 study assessed the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending doses of SLN124 (1.0, 3.0, and 4.5 mg/kg) in healthy volunteers. Twenty-four participants were randomized in three sequential cohorts of eight subjects, each to receive a single dose of either SLN124 or placebo (6:2 randomization), administered subcutaneously. There were no serious or severe adverse events, or discontinuations due to adverse events, and most treatment-emergent adverse events were mild, including transient mild injection site reactions, resolving without intervention. SLN124 was rapidly absorbed, with a median tmax of 4-5 h across all treatment groups, and largely eliminated from plasma by 48 h. Plasma concentrations increased in a greater than dose proportional fashion between treatment groups. In all SLN124 groups, a dose-related effect was observed across iron metabolism markers, and across erythroid markers, SLN124 resulted in increased plasma hepcidin levels, peaking around Day 29, and consequent dose-related sustained reductions in plasma iron and transferrin saturation with decreased reticulocyte production, MCHC, and MCV. Results suggest duration of action lasting up to 56 days after a single SLN124 dose, on hepcidin and hematological parameters of iron metabolism (serum iron and TSAT).

Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

Objectives: The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Design: Retrospective review of medical records. Setting: Private and academic pain clinic practices. Subjects: Chronic noncancer pain patients. Methods: We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. Results: The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Conclusions: Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (<3 mg/d) of morphine. Furthermore, microdose therapy was feasible, safe, and cost-effective in the outpatient setting.

Impact of Laws Regulating Pain Clinics on Opioid Prescribing and Opioid-Related Toxicity Among Texas Medicare Part D Beneficiaries.

BACKGROUND: Pain management clinics are major sources of prescription opioids. Texas government passed several laws regulating pain clinics between 2009 and 2011 to reduce opioid-related toxicity. Understanding the impact of these laws can inform policy geared toward making the laws more effective in curbing the growing epidemic of opioid overdose, especially among the elderly population. OBJECTIVES: To examine the longitudinal association of laws regulating pain clinics on opioid-prescribing and opioid-related toxicity among Texas Medicare recipients. METHODS: The 2007 to 2012 claims data for Texas Medicare Part D recipients were used to assess temporal trends in the percentage of patients filling any schedule II or schedule III opioid prescription, hospitalization for opioid toxicity, and their relationships to the 2009 to 2011 Texas laws regulating pain clinics. We excluded those with a cancer diagnosis. Join-point trend analysis with Bayesian Information Criterion selection methods were used to evaluate the change in monthly percentages of patients filling opioid prescriptions and hospitalization over time. RESULTS: There was a short-lived decline in the monthly percentages of patients who filled a schedule II or schedule III opioid prescription after the 2009 laws regulating pain clinics. The decline lasted about 3 months. Subsequent new laws had no effect on the percentages of patients who filled any opioid prescription or were hospitalized for potential opioid toxicity. Hospitalizations for opioid toxicity were highest in the winter and lowest in the summer. CONCLUSIONS: Changes in the percentages of opioid-prescribing or opioid-related hospitalizations over time were not associated with laws regulating pain clinics.

Comparative effectiveness of pain control between opioids and gabapentinoids in older patients with chronic pain.

ABSTRACT: Gabapentinoid (GABA) prescribing has substantially increased while opioid prescribing has decreased since the 2016 Centers for Disease Control and Prevention Guidelines restricted opioid prescribing for chronic pain. The shift to GABA assumes equal analgesic effectiveness to opioids, but no comparative analgesic effectiveness data exist to support this assumption. We compared GABA to opioids by assessing changes in pain interfering with activities (activity-limiting pain) over time in patients with chronic pain. We used 2017 to 2019 data from a 20% national sample of Medicare beneficiaries diagnosed with chronic pain who initiated a GABA or opioid prescription for ≥30 continuous days and received home health care in the study year. The main outcome was the difference in reduction in pain score from pre- to post-prescription assessments between the 2 groups. Within a 60-day window before-and-after drug initiation, our sample comprised 3208 GABA users and 2846 opioid users. Reduction in post-prescription scores of pain-related interference with activities to less-than-daily pain was 48.1% in the GABA group and 41.7% in the opioid group; this remained significant (odds ratio = 1.29, 95% confidence interval: 1.17-1.43, P < 0.0001) after adjustment for patient demographics and comorbidities. The adjusted difference in reduced pain-related interference score between the 2 groups was -0.10 points on a 0 to 4 scale ( P = 0.01). Gabapentinoid use had greater odds of less-than-daily pain post-prescription, in a dose-dependent manner. Thus, GABA use was associated with a larger reduction in chronic pain than opioids, with a larger effect at higher GABA dosage. Future research is needed on functional outcomes in patients with chronic pain prescribed GABA or opioids.

Access to Medications for Opioid Use Disorder During COVID-19: Retrospective Study of Commercially Insured Patients from 2019-2022.

INTRODUCTION: This study assesses disparities in medications for opioid use disorder in adults with opioid use disorder and examines the associations between state-level COVID-19 lockdown and telehealth policies and medications for opioid use disorder utilization rates during the COVID-19 pandemic. METHODS: This retrospective cohort study of 396,872 adults with opioid use disorder analyzed monthly medications for opioid use disorder utilization rates between January 2019 and June 2022 using data from Clinformatics Data Mart Database. Primary outcome measure was monthly medications for opioid use disorder utilization rates. Variables of interest were patients' demographics and state-level characteristics (telehealth policies for controlled substance prescribing, COVID-19 lockdown policy, and registered buprenorphine providers/100,000). In multivariable analyses, time trend was grouped into four time periods: before COVID-19, early COVID-19, early vaccine, and Omicron-related COVID-19 surge and thereafter. RESULTS: Medications for opioid use disorder rates increased from a 1.2% change in slope monthly on a log scale to 2% monthly from February 2021 to October 2021, after which the utilization rate increased to a lesser degree. Women had 28% lower odds of receiving medications for opioid use disorder than men; Hispanic, Black, and Asian patients had 40%, 34%, and 32% lower odds of receiving medications for opioid use disorder than White patients, respectively. These sex and racial disparities persisted throughout the pandemic. Regional medications for opioid use disorder rate differences, mediated by buprenorphine providers/100,000 state population, decreased during the pandemic. States with telehealth policies for controlled substance prescribing had greater percentages of patients on medications for opioid use disorder (11.7%) than states without such policies (10.4%). CONCLUSIONS: Monthly medications for opioid use disorder rates increased during the pandemic, with higher rates in men, White individuals, and residents of the Northeast region. States with policies permitting telehealth prescribing of controlled substances also had higher medications for opioid use disorder rates, supporting a future expansion of medications for opioid use disorder-related telehealth to improve access to care.

Electronic Real-Time Monitoring Reveals Limited Adherence to Long-Term Opioid Prescriptions in Pain Patients.

Background: Pain management physicians are increasingly focused on limiting prescription opioid abuse, yet existing tools for monitoring adherence have limited accuracy. Medication event monitoring system (MEMS) is an emerging technology for tracking medication usage in real-time but has not been tested in chronic pain patients on long-term opioid regimens. Objective: We conducted a pilot clinical trial to investigate the utility of MEMS for monitoring opioid adherence and compared to traditional methods including self-report diaries, urine drug screen (UDS), and physicians' opinions. Methods: Opioid-maintained chronic pain patients were recruited from a pain management clinic. Participants (n=28) were randomly assigned to either receive MEMS bottles containing their opioid medication for a 90-day period or to continue using standard medication bottles. MEMS bottles were configured to record and timestamp all bottle openings and the number of pills that were removed from the bottle (via measurement of weight change). Results: Participants who received MEMS demonstrated highly heterogenous dosing patterns, with a substantial number of patients rapidly removing excessive amounts of medication and/or "stockpiling" medication. By comparison, physicians rated all participants as either "totally compliant" or "mostly compliant". UDS results did not reveal any illicit drug use, but 25% of participants (n=7) tested negative for their prescribed opioid metabolite. MEMS data did not correlate with physician-rated adherence (P=0.24) and UDS results (P=0.77). MEMS data consistently revealed greater non-adherence than self-report data (P<0.001). Conclusion: These results highlight the limits in our understanding of naturalistic patterns of daily opioid use in chronic pain patients as well as support the use of MEMS for detecting potential misuse as compared to routine adherence monitoring methods. Future research directions include the need to determine how MEMS could be used to improve patient outcomes, minimize harm, and aid in clinical decision-making. Trial Registration: This study was preregistered on ClinicalTrials.gov (NCT03752411).

Medically supervised taper for ultra high-dose opioids with significant comorbidities using a multidisciplinary approach: A case report.

INTRODUCTION: The opioid epidemic and current opioid use guidelines for chronic noncancer pain have resulted in an overwhelmingly large number of patients undergoing opioid tapers. Even though the literature for tapering guidelines is growing, there is little guidance for tapering patients on ultra high-dose opioids. CASE DESCRIPTION: This case report describes in detail the opioid tapering approach used to taper a 53-year-old male with chronic low back pain on a regimen of a morphine equivalent daily dose (MEDD) of 1,990 mg. Patient reported many side effects such as chronic nausea, irritability, psychomotor depression, and functional impairment. He was admitted for a medically supervised opioid taper for 12 days. RESULTS: The patient was discharged with an MEDD of 392 mg with additional taper as an outpatient to an MEDD of 200 mg. Adequate pain relief and resolution of side effects were achieved without the patient reporting significant withdrawal symptomatology in the outpatient setting.

Prescribing of Gabapentinoids with or without opioids after burn injury in the US, 2012-2018.

Burn injury pain manifests as a combination of inflammatory, nociceptive, and neuropathic features. While opioids are the mainstay of burn pain management, non-opioid medications, such as gabapentinoids, have also been considered as they target the central nervous system. Increased opioid adverse events and overdose deaths in the United States led to the 2014 and 2016 guidelines to reduce opioid prescribing and consider alternatives, such as gabapentinoids. In the context of burn, the rate of gabapentinoid prescribing at the national level is unknown and it is unclear whether any shift has occurred in prescribing practices over time. We conducted a population level cohort study of adult burn patients from 2012 to 2018 to evaluate the rates and determinants of gabapentinoid prescribing, with and without opioids. Of 98,001 patients with burn, 22,521 (22.98%) received opioids and/or gabapentinoids (GABA). GABA represented 2.4% of prescriptions in 2012, but increased to 7.2% by 2018, while GABA-opioid co-prescriptions increased from 2.3% to 5.1%. The rate of increase in GABA prescriptions was higher for those aged 50-65 years or residing in the South. After adjustment, GABA was 44% more likely to be prescribed in 2017 and 2018 compared to 2012 and 2013, opioids were 38% less likely, while co-prescribing did not show a statistically significant change. Our study showed a modest increase in gabapentinoids' outpatient prescribing for burn patients after the 2014 and 2016 guidelines, indicating more opportunities for prescribers to expand non-opioid pain management in this population.

Pulsed radiofrequency V2 treatment and intranasal sphenopalatine ganglion block: a combination therapy for atypical trigeminal neuralgia.

Trigeminal neuralgia (TN) is a chronic condition affecting the fifth cranial nerve and resulting in sporadic intense burning and shock-like pain lasting for seconds to minutes that can be incapacitating to patients. Atypical TN includes additional features such as continuous pain and sensory disturbances in the area innervated by one or more branches of the trigeminal nerve. Documented cases of TN have dated back to the 18th century. Today, there are roughly 140,000 people suffering with this condition in the U.S.A. Conventional treatments for this disorder include medical management with nonconvulsants such as carbamazepine, which decrease the nerves response to peripheral stimulation. These agents have good initial pain relief, but relief rates fall off dramatically over the long-term. Recently, methadone has shown promise as a pharmacologic adjunct to patients with intractable neuropathic noncancer pain, including patients suffering from TN. Cases refractory to medical management can be treated with surgical microdecompression or minimally invasive procedures such as radiofrequency (RF) treatment. Pulsed RF (PRF) is a method gaining interest as it is delivered in pulses, allowing adequate time for dissipation of heat and energy resulting in less damage to surrounding structures. This case report describes the successful treatment of atypical V2 TN refractive to medical management requiring PRF treatment, a sphenopalatine block series, and low-dose methadone.

Quantification of Opioid Prescription Practice Changes Due to Hydrocodone Combination Product Rescheduling in an Academic Pain Clinic.

PURPOSE: To determine the effect of rescheduling on prescription practices in a large academic hospital-based multidisciplinary practice comprising anesthesiologist-trained pain physicians. PATIENTS AND METHODS: We examined the number of HCP prescriptions written and quantity of tablets prescribed during a 6-month period prior to rescheduling and compared this with a 6-month period 1 year after rescheduling. We also examined the changes in prescription of tramadol and acetaminophen with codeine from one period to the next. RESULTS: Our pain clinic conducted 3,320 office visits during the 6-month period prior to HCP rescheduling and 6,003 office visits in the 6-month period 1 year after rescheduling. The charted data from each of these visits were used for our analysis. The mean number of tablets of HCPs prescribed per patient decreased from 318.48 in the pre-period to 242.27 tablets in the post-period, while the mean number of HCP prescriptions per patient decreased from 2.24 to 1.84. The mean number of acetaminophen with codeine tablets prescribed per patient increased from 3.46 to 15.27 in the pre- and post-period. Similarly, the mean number of tramadol tablets per patient increased from 47.33 to 61.97 in the pre- and post-period. The mean number of acetaminophen with codeine and tramadol prescriptions per patient increased from 0.02 to 0.15 and 0.38 to 0.51 in the pre- and post-period, respectively. In the 6-month post-period, fewer new patients were started on opioids compared to the 6-month pre-period, 16% and 27%, respectively. CONCLUSION: Our study showed a significant decrease in the mean number of HCP prescriptions written per patient, as well as a decrease in the mean number of HCP tablets prescribed. Pain physicians in our clinic increased the number of prescriptions for the non-HCPs. The number of acetaminophen with codeine and tramadol tablets prescribed significantly increased. Therefore, the rescheduling of HCPs has profoundly impacted practices within this academic pain clinic.

Alcohol neurolysis of the sciatic and femoral nerves to improve pressure ulcer healing.

UNLABELLED: Successful pressure ulcer treatment is challenging and is often plagued with prolonged hospitalizations, multiple surgeries, and high recurrence rates. Pressure ulcer secondary to spinal cord injury is further complicated by spasticity, which contributes to both ulcer continuance and healing. This report illustrates the use of neurolytic regional techniques for spasticity control and pressure ulcer healing. CASE REPORT: We present our experience with a paraplegic man who suffered from chronic right trochanteric and ischial pressure ulcers that failed to heal despite surgical and conservative treatment. We report the successful treatment of knee and hip flexor spasticity with a femoral and sciatic alcohol neuroablation technique. It was not until the successful control of his lower extremity spasticity that the pressure ulcers showed signs of healing. Neuroablation nay be considered for spasticity control when more conservative approaches fail or are not feasible.

Ultrasound-determined landmarks decrease pressure pain at epidural insertion site in immediate post-partum period.

BACKGROUND: Women have blamed epidurals for their post-partum back pain for decades. Survey-based studies have shown similar incidence of chronic back pain between women who delivered with epidurals compared to those who did not. However, epidural insertion site pain has yet to be evaluated by a quantitative measure: pressure pain threshold (PPT). Algometer measured PPT has been shown to be accurate and reproducible in acute, chronic, and postoperative pain studies. This study determines the effect of ultrasound-based landmarks on the PPT at the epidural insertion site in the post-partum period. METHODS: Participants were randomized into either the ultrasound or sham groups. In addition, a non-randomized control group (no epidural) participated. Ultrasound of the lumbar region was used to mark mid intervertebral levels in the US group but not in the sham group. Epidural were placed using the marks in the US group or palpated bony landmarks in the sham group. PPT at each intervertebral space measured before and after the use of epidural. RESULTS: Epidural placement did significantly decreased PPT in US (68%) and US sham (79%) groups and less in the control group (21%). US group showed decreased PPT only at insertion site whereas US sham group also showed decreased PPT at insertion site and adjacent levels. CONCLUSIONS: We showed that epidural placed with ultrasound-determined landmarks not only improves the success of epidural placement but also minimizes the number of intervertebral levels with decreased PPT.

Programmable intrathecal pumps for the management of chronic pain: recommendations for improved efficiency.

The management of chronic pain can be very challenging. Often, physicians employ intrathecal (IT) drug delivery systems as a last resort to relieve intractable pain. The system consists of an implantable pump that stores and delivers medication through a catheter to the IT space. Programmability is achieved by positioning an external devise over the implanted pump to change the mode of drug delivery. The innovations in programmable IT drug delivery systems are expanding more rapidly than ever before. Unfortunately, the rapid expansion is accompanied by a lack of prospective randomized trials examining these new options. In an effort to improve results and reduce side effects, publications by experts or expert consensus panels provide guidance for the community. The purpose of this article is to provide a summary of high interest topics in recent publications.

A large animal neuropathic pain model in sheep: a strategy for improving the predictability of preclinical models for therapeutic development.

BACKGROUND: Evaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large animals are limited. To address this deficiency, we developed a neuropathic pain model in sheep, which shares many anatomical similarities in spine dimensions and cerebrospinal fluid volume as humans. METHODS: A neuropathic pain state was induced in sheep by tight ligation and axotomy of the common peroneal nerve. The analgesic effect of intrathecal (IT) morphine was investigated. Interspecies comparison was conducted by analyzing the ceiling doses of IT morphine for humans, sheep, and rats. RESULTS: Peroneal nerve injury (PNI) produced an 86% decrease in von-Frey filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted for the 8-week test period. Compared to the pre-injury, sham, and contralateral hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED(50)) for injured PNI hindlimb was 1.8-fold larger and E(max), the dose that produces maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT morphine ceiling dose by allometric scaling. This is in contrast to the approximately 10-fold lower morphine ceiling dose predicted by the rat spinal nerve ligated or spared nerve injury models. CONCLUSION: PNI sheep model has a fast onset and shows stable and long-lasting pain behavioral characteristics. Since the antinociceptive properties of IT morphine are similar to those observed in humans, the PNI sheep model will be a useful tool for the development of analgesics. Its large size and consistent chronic pain behavior will facilitate the development and evaluation of surgical intervention and gene therapy. The PNI sheep pain model provides us with the opportunity for multi-species testing, which will improve the success of clinical trials.

Intrathecal catheter-syringe adaptor for short-term intrathecal analgesia with an externalized pump: a case report.

BACKGROUND: In most patients, cancer pain is effectively treated with conservative medical management consisting of oral and/or transdermal analgesics. Cancer patients tend to fail conservative medical management near the end of their life expectancy, thus requiring alternative routes of analgesia such as intravenous, epidural, or intrathecal. The intrathecal route provides the most effective analgesia due to the close proximity of the opioid receptors in the spinal cord. Though there are many techniques that exist for intrathecal drug delivery, complications can limit effectiveness such as infection, bleeding, cerebrospinal fluid (CSF) leaks, post-dural puncture headaches (PDPH), pump and/or catheter malfunctions, or limitations of technical expertise. Therefore, an important goal in palliative cancer pain therapy is to use equipment that is going to have the fewest number of complications and will be the most familiar to the health care providers. We describe the combination of the Medtronic Indura 1P catheter, which has the least catheter-related complications and can be used with any external drug infusion pump. These are regular infusion pumps that the health care workers are familiar with so they can provide excellent and efficient service to the patient. METHODS: In an operating room, the intrathecal catheter was placed using sterile technique under fluoroscopic guidance. The epidural space was identified with loss of resistance technique. Then the introducer needle (supplied in the Indura 1P catheter kit) was advanced until free-flowing CSF was obtained. The spinal catheter was advanced into the intrathecal space through the introducer needle to lumbar 2-3 level. The catheter was tunneled subcutaneously 10 cm lateral to the catheter exit site. A syringe filling device was inserted into the catheter opening and was secured with silk suture. A luer lock syringe was attached to the syringe filling device and CSF was aspirated. The syringe filling device was capped and later attached to an external drug infusion pump. RESULTS: We report the successful use of the Medtronic Indura 1P, one piece intrathecal catheter, connected to the external drug pump for a 3 week period in a patient with metastatic cervical cancer for palliative pain control. LIMITATIONS: Case report only. CONCLUSION: This technique is simple to perform by pain specialists. The catheter modification allows the use of the Medtronic intrathecal catheter with standard external drug infusion pumps. This facilitates the patient's care in the hospice setting.

Pulsed radiofrequency treatment of lower extremity phantom limb pain.

BACKGROUND: Phantom limb pain can be challenging to treat. We present a patient who developed severe phantom limb pain after revision of her lower extremity amputation due to the continued progression of peripheral vascular disease. Multiple treatment modalities had been tried without success. Pulsed radiofrequency has been successfully used to manage a number of pain syndromes. OBJECTIVE: The present case report describes the use of pulsed radiofrequency treatment for phantom limb pain. METHODS: The authors initially preformed regional blocks of femoral and sciatic nerve with 0.375% bupivicaine 15 cc and 50 microg clonidine to control the patient's pain. The blocks provided good pain relief but with limited duration. Based on reports of prolonged pain relief provided by pulsed radiofrequency treatment for other chronic pain conditions such as lumbrosacral spondylosis, we decided to apply this treatment to the patient's sciatic nerve. The patient underwent pulsed radiofrequency treatment with 2 cycles of 120 seconds at 42 degrees, pulse rate of 2 pulse/second, and pulse duration of 20 milliseconds. RESULTS: Our report shows that the sciatic nerve block with bupivicaine and clonidine, initiated approximately 3 years after amputation, produced modest short-term relief. The pulsed radiofrequency treatment resulted in long-term relief of phantom limb pain. The patient was able to wean herself off all oral medications and has been pain free for 4 months.

Nucleotide triphosphatase activity of the N-terminal nucleotide-binding domains of the multidrug resistance proteins P-glycoprotein and MRP1.

The multidrug resistance proteins P-glycoprotein (Pgp) and MRP1 are drug-efflux pumps. In this study, we compared the nucleotide triphosphatase activities of the isolated N-terminal nucleotide binding domains (NBD1) of Pgp and MRP1, and explored the potential role of the phosphorylation target domain of Pgp on the regulation of Pgp NBD1 ATPase activity. We found that: (1) the NBD1s of Pgp and MRP1 have ATPase and GTPase activities, (2) the K(m)s of Pgp NBD1 for ATP and GTP hydrolysis are identical, while the K(m) of MRP1 NBD1 for ATP is lower than that for GTP, and (3) phosphorylation of MLD by PKA or PKC produces a marginal increase of V(max) for ATP hydrolysis, without affecting the affinity for ATP. These results show efficient GTP hydrolysis by the NBD1s of Pgp and MRP1, and a minor role of phosphorylation in the control of Pgp NBD1 ATPase activity.