August 2010: CRPS Clinical Trials, Part Two

I apologize for leaving you hanging after "Part One." Here are the remainder of the clinical trials currently seeking volunteers, or about to enlist participants. 

Some of these studies have been listed... forever, and are also past their own termination dates, so I have not listed them.

As usual, keep a sharp eye for the details -- where the study takes place, eligibility requirements, exclusion criteria, type of treatment (if any).  In a few cases, it might be worthwhile to note who is backing or funding the study.

Good luck!

** The Efficacy of Motor Cortex Stimulation for Pain Control
OBJECTIVE:  .
Each of these groups of 6 patients (total of 18) will be studied independently and all patients will be implanted with a motor cortex stimulation system. They will be randomised to either a regular or low stimulation setting in the two arms of the study. Each arm will last 3 months...
The aim of this study is to examine the effectiveness of this modality in a controlled blinded manner, which has not been done in previous studies. There are two primary purposes of this study. The first is to compare two different stimulation paradigms: "high" level stimulation (i.e. stimulator activated 'on' for 10 minutes, 'off' for 2 hours; presumed therapeutic dose); versus "low" stimulation ('on' for 1 minute, 'off' for 6 hours; presumed subtherapeutic dose), in a prospective blinded crossover study design.


The second purpose of this study, is to examine the outcome of MCS in three different pain groups. These are:
1.Unilateral upper extremity neuropathic pain such as brachial plexus avulsion, stump pain or phantom limb pain
2.Neuropathic deafferentation facial pain
3.Upper extremity complex regional pain syndrome (CRPS)
 
Inclusion Criteria:

1.Diagnosis in one of the following three categories:
◦Unilateral upper extremity neuropathic pain such as phantom limb pain, stump pain or brachial plexus avulsion
◦Neuropathic deafferentation facial pain
◦Upper extremity complex regional pain syndrome (CRPS)
2.Pain is refractory to conservative methods (e.g. medications, regional blocks) as reviewed by a chronic pain clinical physician
3.Patient is considered a good candidate for neurosurgery, i.e. no other medical problems that would preclude surgery
4.Patients who are willing to provide informed consent.

Exclusion Criteria:
1.Patients who are not considered medically fit for neurosurgery.
2.Patients who have not exhausted conservative methods of pain control, prior to considering motor cortex stimulation.
3.Patients who are not able to provide informed consent.
4.Patients unable to have magnetic resonance imaging (MRI).

CONTACT: Robert M Brownstone, MD, PhD 902 473 6850 rob.brownstone@dal.ca
Dalhousie University, Queen Elizabeth II Health Sciences Centre CANADA

Publication perhaps of interest: TEMPORARY SPINAL STIMULATION FOR PERIOPERATIVE MANAGEMENT OF CRPS

Dr. Ian Beauprie. MD FRCPC: Dr. Rob Brownstone, MD, PhD, FRCS; Dr. Justin Paletz, MD, FRCS, QEII Health Sciences Centre, Halifax, Nova Scotia -- presented at the Canadian Pain Society Conference, March/April 2010

Select publications from Dr. Brownstone's Lab (Motor Control Laboratory), Dalhousie Univ, Halifax, Nova Scotia. CANADA: click here.

** Analysis of Photoplethysmographic Signal in Lumbar Sympathetic Block (park001)
Historical versions of this study are available here.
[Excuse the intrusion of this blogger's opinion, here, but I have qualms about a study that perpetuates the notion and practice of sympathetic blocks as diagnostic for CRPS.]
Inclusion Criteria:

•Physically examined for complex regional pain syndrome on lower extremity,
•Scheduled for diagnostic lumbar sympathetic blockade.
Exclusion Criteria:
•Graded as ASA 3 or higher,
•Below 18 or above 70 years of age, or
•Had any other contraindication for regional anesthesia.
LOCATION:  REPUBLIC OF KOREA, Clinical Research Institute, Seoul National University Hospital
NO CONTACT INFO LISTED

** Peer Mentorship: An Intervention To Promote Effective Pain Self-Management In Adolescents
DETAILED DESCRIPTION/PRESENTATION OF PRELIMINARY DATA:
Background:

Chronic intractable non-malignant pain, including such functional disorders as irritable bowel syndrome is now recognized as a significant problem in children and adolescents, with potential long-term impact on the child's physical, social, and academic functioning, as well as on the family as a whole. A recent study of more than 5000 Dutch school children under 18 found that more than 25% reported suffering recurrent or continuous pain for more than 3 months, with the prevalence increasing with age; and a survey of 735 German children aged 10-18 using a modified version of the same instrument found the same for 45.5%. The most common types of pain in these two studies were headache, abdominal pain, limb pain, and back pain. This data would appear to confirm earlier estimates that recurrent headache, including migraine, occurs in 11% to 26% of children ages 7-15; recurrent abdominal pain in 10-15% and recurrent limb pain in 4-18% in children ages 7-15. Many such children apparently continue to function effectively, attending school and continuing normal activities, with medical intervention only for acute episodes. A smaller, but significant, number, however, find themselves unable to self-manage their pain. They become patients with chronic pain and disability, falling into a cyclical pattern of pain, impaired functioning in physical, school, social, and even family and self-care domains, "doctor-seeking" and over-utilization of medications, and psychosocial distress, including anxiety and depression.

Functional impairment, particularly in academic work and social participation, is likely to have long-term effects on the individual's quality of life, even aside from the possibility that pain and physical limitations may persist into adulthood. Several well-designed studies using quantitative measures have provided evidence that impaired functioning in children with chronic pain is strongly associated with psychosocial distress and with lower quality of life. In particular, children with unexplained chronic pain, pain not associated with an organic diagnosis, often report significant dysfunctions in normal activities, such as schoolwork, sleep, family activities, and athletic activities. But, although impaired functioning is a major factor in lower quality of life for children with chronic pain, we still know relatively little about the prevalence and severity of functional impairment, why some children experience more limitations than others, and which treatment interventions are the most effective in improving function.

The available evidence also indicates that children show different levels of adjustment to chronic pain over time. Chronic idiopathic musculoskeletal pain has been shown to persist in 59% of cases for as long as nine years; in this study, the authors found the children to have pain and disability levels comparable to children with juvenile chronic arthritis, but lower levels of psychosocial functioning. Hunfeld, Perquin, and colleagues in Rotterdam have traced the persistence of chronic benign pain in 30-45% of cases for up to two years and three years, with no increase in intensity or frequency. In the latter study, open-ended interviews elicited information about functioning and coping skills, and identified continuing problems with physical activity, mental concentration, social interaction, and psychological stress (becoming "moody"), particularly when the pain was severe. The researchers found, however, that several children had developed their own strategies to maximize functionality despite the continuing pain: "…pain had become part of the daily lives of several adolescents, who structured their activities and sleeping hours to prevent aggravation of pain". A recent cluster analysis of 117 children with chronic pain divided them into three groups on the basis of a set of psychosocial and behavioral measures: those who were highly distressed and disabled; those who showed low levels of distress and disability; and those who showed only moderate levels of distress and disability, but whose family environment scored low on cohesion.

Although several factors may account for children's differential ability to function and to adjust to persistent chronic pain, the child's sense of self-competence has been identified as a key variable in recent literature. Claar and colleagues, for example, found that in adolescents and young adults with irritable bowel syndrome, the relationship between pain and functional disability was moderated by the individual's sense of academic, social, and athletic competence. The concept of self-competence (a general sense of mastery) overlaps with that of self-efficacy (a task-specific sense of mastery), developed by Albert Bandura in the late 1970s and early 1980s 18. The concept of self-efficacy suggests an explanation for the relationship between coping skills, perceived ability to cope, and reduction in physical and psychological disability. Bandura argued that a sense of self-efficacy enables the individual to persist even with a task of great difficulty until it is mastered, to reject negative thoughts and to "bring cognitive or cerebral productions into being" that will assist in achieving the goal.

To summarize briefly, impaired functioning in all domains is a major and potentially a long-term problem for children with recurrent or chronic pain and their families, which are a significant segment of the American population. Children show significant variations in their ability to cope with pain and continue to function, and some children learn better functioning over time. The child's own sense of self-competence, or task-specific self-efficacy, is one important factor which may reinforce or moderate the child's functioning. Functional disability is clearly associated with psychosocial distress. But these factors are also mutually reinforcing; while children with more psychosocial distress may have more problems functioning with pain, certainly children who experience pain and attendant functional problems are likely to react with anxiety and/or depression.

Current Therapeutic Interventions: When chronic pain can not be fully alleviated, the optimal goal is for the patient to learn effective ways to continue functioning and to self-manage pain; several therapeutic programs have been developed, based on theories of health behavior change, to assist the patient in this process. The earliest of these, the operant learning model developed by Wilbert Fordyce and colleagues in the late 1970s, demonstrated that individuals could be induced to alter their behavior - specifically, to engage in active exercise and limit dependence on medication - in response to social and other forms of positive reinforcement. Fordyce's program proved helpful to many patients, but was criticized for its determinist emphasis on observable behavior and disregard of the fact that patients are "active information processors", and that their behavior is not merely a response to learned cues but shaped by cognitive processes, such as expectations of increasing pain or anxieties about physiological harm.

The revised therapeutic programs that developed in response to these criticisms drew on overlapping models linking health beliefs to health behavior and to self-efficacy as described by Bandura. These new models rely on an expectancy-value theory of behavior; that behavioral change is not a simple learned response to reinforcement, but that learning is influenced by the individual's cognitive belief (expectancy) that s/he will be able to change functioning with positive consequences (self-efficacy) and by his/her expectations (values) of the potential benefits of and barriers to behavioral change. Thus the new therapeutic programs, the most well-known and widely practiced of which is cognitive-behavioral therapy (CBT), seek to mediate behavioral change through cognitive relearning. The cognitive behavioral therapist uses a number of methods -- including education about pain, verbal reinforcement for positive cognitions and actions, biofeedback, group therapy allowing patients to observe and learn from each other, and teaching of cognitive tools to repress negative thoughts -- to help the patient develop positive expectations of behavior change, minimize negative expectations, and internalize the conviction of his/her own ability to overcome barriers and effectively self-manage pain In effect, the patient becomes the agent of change.

CBT has been shown to be effective in controlled trials of treatment pain in cancer patients; of chronic low-back pain; of osteoarthritic knee pain; of sickle cell disease; of pediatric migraine; and of recurrent abdominal pain in children. CBT with family involvement has been found to be an effective intervention for adolescents with chronic pain and chronic fatigue 31-33. Flor, Fydrich, and Turk's 1992 analysis of 65 studies of multidisciplinary treatments for chronic low back pain in adults, covering a number of variants of cognitive, behavioral, and coping skills training packages, noted that many of the studies were "marginal" in quality, but nevertheless demonstrated that these methods were superior to no treatment and to single-modality treatment -- medical or physical therapy -- in decreasing pain and impairment, improving mood, promoting return to work, and decreasing health services utilization. "Even at follow up, patients...are functioning better than 75%" of control groups; the findings of efficacy are "quite impressive". A recent systematic review of behavioral treatment for low back pain again found only six studies "of high quality". The authors nevertheless thought the evidence strong that behavioral therapy had at least "a moderate positive effect" on pain intensity and "small positive effects" on functional status; but they noted that "it is still unknown what type of patients benefit most" from behavioral therapies.

A well-designed intervention, it appears, is not enough: not all patients will benefit from CBT. As Dennis Turk, the leading exponent of CBT, has stated, patient motivation is at least one of the critical factors in successful outcomes of this therapeutic model. Jensen and colleagues have recently proposed a cogent general model that integrates the varied theoretical approaches to describe a dynamic process that pivots on this concept of motivation, or readiness to change. An individual's readiness to change, they argue, is essential to his/her ability to learn successful pain self-management through new behaviors; and readiness is a dynamic function of 1) his/her perceived importance of the change (beliefs of the costs and benefits of change, past experience with change (learning history), and current contingencies (availability of social and material support) and 2) his/her self-efficacy beliefs (personal experience, modeling provided by others, verbal persuasion, and perceived barriers). They suggest some clinical approaches for enhancing readiness and promoting change, including encouragement to practice self-management; allowing the patient to observe other pain patients practice self-management; support of positive beliefs and non-judgmental non-support of negative beliefs; and development of a plan to address real or perceived barriers; and they call for research into interventions along these lines to enhance motivation.

Another formulation recently proposed by Sharp stresses the patient's cognitive activity in appraising and evaluating his or her pain, and its ongoing and interactive effects on mood, behavior, and somatic focus. The patient's initial response to the pain is a function of cultural beliefs, learning history, and current contingencies, he argues, but then is continually reinterpreted with ongoing events. In particular, anxiety about recurrent pain and avoidance of activity that might cause pain will help to perpetuate the patient's hypervigilance for signs of recurring pain (as described by Eccleston and Crombez) and his/her perceived inability to manage the pain. Moreover, Sharp contends that this attitude of "learned helplessness" may be perpetuated by physicians who have failed to offer helpful treatment or even to confirm the physical reality of the patient's suffering. "That is, patients could start to believe that 'nothing has worked so far so why would any future treatment help?" A patient who has reached this point is likely to have a negative assessment both of the benefits of pain self-management and of his/her own ability or self-efficacy to learn these skills, and will therefore show a lack of readiness to change.

In this study, we will consider adolescent pain patients and whether a new type of innovation can promote their readiness to change and to learn pain self-management skills, that will promote positive outcomes in pain reduction and improved functioning.

Findings from our Current Research: Our interdisciplinary group, comprised of researchers from anthropology, history, pediatrics, psychology, and sociology, has collected quantitative and interview data on 74 adolescent children presenting between 2003 and 2006 to the Pediatric Pain, Pediatric Gastroenterology, and Pediatric Neurology Clinics with recurrent or persistent pain. We have completed preliminary analysis of the qualitative data for a subset of 37 (28 girls and 9 boys, average age 13.97) for whom intake and six-month follow-up data was obtained. These children reported suffering pain for periods ranging from one month to "all my life": the average computed duration was 53.6 months, or about 4.5 years. All of them had seen at least one physician prior to referral to UCLA and the majority had seen three or more.

The children's levels of functioning varied considerably on the quantitative measures, but the evidence from the long, semi-structured interviews (conducted prior to the first Clinic appointment and at 6 months) shows that virtually all were distressed by some level of impairment. Those who had had pain for several years reported that pain had become part of daily life and that they adjusted their lives around it: Many of the children also stated that their unexplained chronic pain, which a series of doctors had not been able to diagnose, had given them a sense of isolation and difference from others, and a sense of powerlessness, that contributed to their distress:

Those children seen in the Pediatric Pain Clinic (28, or 76% of the 37) were given recommendations to choose one or more of a list of complementary and alternative medicine (CAM) providers who work with the clinic; these include several who teach pain self-management skills, including a physical therapist, yoga therapist, biofeedback trainer, and guided imagery/hypnotherapist. These recommendations were made in addition to those for tests, changes in medication or other therapies. Children seen in the GI or Neuro Clinic might be given a recommendation for PT or another CAM treatment, but it was not a standardized part of the treatment plan. At the follow-up interview, the children were asked whether their pain and functioning had improved, and also to talk about their participation in any of the CAM therapies:

Better, pain improved or resolved by medication change - 8; 22%
Better, participation in active CAM had helped - 8; 22%
Better, medication change and participation in an active CAM therapy - 4; 11%
Same, meds had not helped, no interest in CAM - 6; 16%
Same, meds had not helped, CAM not tried because not recommended or because of reimbursement issues - 5; 13%
Same, meds had not helped, child tried CAM but did not persist - 2; 6%
Worse, meds had not helped, no interest in CAM - 1; 3%
Worse, meds had not helped, CAM too expensive - 1; 3%
Worse, meds had not helped, child tried CAM but did not persist - 1; 3%
Worse for other reasons (intervening surgery had increased pain) - 1; 3%

These findings are not presented as supportive evidence of the benefits of CAM therapy. Rather, they indicate, that, in this group of children, aside from a small group helped by a medication change and one outlier case, those who were self-motivated to participate in a therapy that taught them active self-management consistently reported better outcomes than those who were not self-motivated or who were unable to do so.

Why did 16 of the children choose not to participate or persist in participating in recommended CAM therapy? One possible explanation is that they lacked confidence that a new therapy will work when many others have failed to work and believed that their pain was a different and intractable problem that doctors did not know how to treat and that they could not manage themselves. Another is that they were not given the opportunity to observe others; were not given sufficient reinforcement from family or other significant contacts for participation; and were not helped to overcome any perceived barriers to access.

On the basis of this preliminary data, considered in the light of current theoretical models, we propose the following hypotheses:
•Adolescents who participate actively in learning a pain-management skill will show more improvement in pain and functioning at 2 and 4 months than those who do not.
•Adolescents who lack peer support for learning a pain management skill will not follow through with learning such a skill without further reinforcement, even if recommended as part of a treatment plan.
•Adolescents may be helped to adhere to treatments that involve learning a pain management skill which will improve their pain and functioning by talking to others who have learned such a skill; by receiving ongoing positive reinforcement; and by being helped to overcome perceived barriers.

We propose to test our hypotheses through a trial of a peer mentorship intervention, using trained adolescents who have successfully learned pain management skills as mentors. The mentor will help to relieve the child's sense of isolation and difference by relating their similar experiences, provide models of successful skill learning and reinforce the mentored subject's participation in skill learning activities.

Qualifying conditions:
•Irritable Bowel Syndrome (IBS)

•Functional Abdominal Pain
•Fibromyalgia
•Complex Regional Pain Syndrome (CRPS)
•Myofacial Pain
•Chronic Daily Headaches
•Migraine Headaches
•Chronic Pain

[I'm sorry... but I do have qualms about lumping CRPS in with conditions of a functional origin...]
INTERVENTION:  Subjects in this condition receive 10 sessions over 8 weeks (2 sessions for the first 2 weeks, 1 session per week for the remaining 6 weeks) with a mentor presenting information on pain self-management and coping techniques, as well as discussing concerns and feelings with the subject receiving the intervention. Information is presented on slides via internet connected home computer. Mentor-mentee interaction is conducted via telephone on a conference call line with a doctoral level psychologist monitoring call for safety of all parties.

MENTOR Criteria
Inclusion criteria:
•between the ages of 14 and 18
•any patient who has been successfully treated in the UCLA Pediatric Pain Program
•access to telephone
•access to internet enabled computer

MENTOR Exclusion criteria
•younger than 14
•older than 18
•new patient
•no access to telephone
•no access to internet enabled computer

MENTEE CRITERIA
Inclusion Criteria:

•chronic pain diagnosis
•between the ages of 12 and 17
•access to telephone
•access to internet enabled computer
•new to UCLA Pediatric Pain Clinic
•plans to utilize program CAM therapies

Exclusion Criteria:
•already utilizing UCLA Pediatric Pain Program CAM therapies
•unable to read, speak, or understand english
•younger than 12 or older than 17
•no access to telephone
•no access to internet enabled computer
•not new patient to UCLA Pediatric Pain Clinic
•does not plan to utilize program CAM therapies

CONTACTS:
Contact: Lonnie K Zeltzer, MD 310-825-0731 LZeltzer@mednet.ucla.edu
Director of UCLA Pediatric Pain Program, UCLA Department of Pediatrics

Contact: Jennie CI Tsao, Ph.D. 310-825-0731 JTsao@mednet.ucla.edu

**  Regional Anesthesia Military Battlefield Pain Outcomes Study (RAMBPOS)
The purpose of this study is to examine the short and long-term benefits of implementing early regional anesthesia techniques for pain control after a major traumatic injury to one or more extremities during combat in the Iraqi/Afghanistan war, including the effects on acute and chronic pain, quality of life, and mental health.

BACKGROUND:

Adequate pain management for combat casualties balances the need for emergent, life-saving care with the urgency to remove soldiers from harm's way. Control of pain in traumatic battlefield situations may be impossible until safe evacuation to a surgical facility is achieved and a wounded soldier can receive general anesthesia. Recent evidence suggests that neural plasticity in the central nervous system coupled with hyperstimulation of central neuronal pathways lead to neuropathological remodeling. This neural rewiring may result in chronic pain for patients who have experienced severe, unrelieved acute pain. In addition, the stress of combat along with the suffering of prolonged uncontrolled pain may contribute to psychological disorders, such as post-traumatic stress disorder, depression, and substance abuse.

OBJECTIVE:
The purpose of this study is to evaluate the effect of early and aggressive advanced regional anesthesia on the chronic neuropathic pain, health related quality of life, and mental health of OEF/OIF veterans who have suffered a major limb injury in combat. An additional aim of this study is to quantify and characterize the short-term and long-term effects of traumatic combat limb injuries on post-injury acute pain, chronic pain, health related quality of life, functional status, social reintegration, psychological adjustment, and substance abuse behaviors in a population of injured military personnel.

METHOD:
This study employs a cohort repeated measures study design involving prospective data collection at scheduled intervals. Interviews with participants provide data on pain outcomes, psychiatric morbidities, and quality of life. Follow up evaluations conclude at the two year anniversary of the start of combat injury rehabilitation. Medical records information collected retrospectively from armed services treatment facilities provide data on the use of pain management therapies as well as individual responses to regional anesthesia.

IMPLICATIONS FOR RESULTS:
The findings of this study may impact the clinical field by providing information on the effectiveness and benefits of early advanced regional anesthesia for chronic pain control. This study may also provide data to determine whether regional anesthesia pain treatments prevent or reduce the development of psychological maladjustment disorders such as post-traumatic stress disorder, depression, and substance abuse in a population of military personnel with combat limb injuries.



Procedure: Regional Anesthesia


Subject received regional anesthesia to affected limb(s) within 72 hours of traumatic event.
•1 Soldiers with one or more mangled or amputated limbs from the Iraq/Afghanistan war aggressively treated with regional anesthesia for pain control.

Intervention: Procedure: Regional Anesthesia
•2 Soldiers with one or more mangled or amputated limbs from the Iraq/Afghanistan war receiving standard treatment for pain control.

ELIGIBILITY CRITERIA:
Inclusion Criteria:

•Major injury in one or more extremities requiring hospitalization and inpatient rehabilitation.

Exclusion Criteria:
•Major head trauma,
•Cognitive deficits,
•Inability to concentrate
•Poor judgment and impulse control,
•Substantial hearing loss
•Bilateral upper extremity amputation with no alternate means to complete the survey forms
 
CONTACTS:
(Dept of Veterans Affairs)
Yolanda S Williams, MPH (215) 823-5800 ext 2774 yolanda.williams5@va.gov [Pain Management Service]
Holly Luu, BA (215) 823-5800 ext 6506 holly.luu@va.gov

•Walter Reed Army Medical Center

•Brooke Army Medical Center
** Efficacy of Etoricoxib on Peripheral Hyperalgesia

This study is not yet open for participant recruitment.
[Does anyone else wonder if Dr. Scott Reuben's criminal fraud perpetrated on the medical (pain management) community makes this study more important/necessary than one would expect?  The good doctor, in case you were wondering, is in prison for a whopping... SIX MONTHS.]

The purpose of the study is to determine the efficacy of etoricoxib on pain patients. The investigators assume that patients with neuropathic pain will have greater pain relief then patients on placebo.


Detailed Description Animal experiments analysing anti-hyperalgesic effects of Coxibs show inconsistent results due to different used dosages and varying different pain models. Theoretical the use of NSAIDs is rational, particularly of Coxibs as a part of the neuropathic pain management. But in the newest topical review, there is no valid information available about the effectiveness of these drugs in human neuropathic pain models or in patients with different underlying mechanism, e.g. with or without hyperalgesia.

Conditions accepted:
•Causalgia

•Polyneuropathy
•Postherpetic Neuralgia
•Peripheral Nerve Injury
•Radiculopathy
ELIGIBILITY REQUIREMENTS:
Inclusion Criteria:

•Patients over 18 years with
•Persistent moderate or severe pain (> 4 on NRS (1..10)) at rest (average of three daily assessments using a diary for at least two days) .
•Neuropathic pain associated with a clinical and neurologically proven peripheral nerve injury, radiculopathy, postherpetic neuralgia or polyneuropathy or CRPS
•One of the two following QST phenotypes at the baseline assessment:
◦signs of peripheral hyperalgesia (that means, pathological decreased heat pain threshold and/or pathological decreased muscle pain threshold)
◦without signs of peripheral hyperalgesia (no pathological decreased heat - and/or muscle pain threshold)
•Patients of both gender
•Signed consent form
•Patients with the ability to understand and follow the instructions of the doctor

Exclusion Criteria:
•Excluded will be patients Parkinson's disease or a history of cerebral vascular insult or nerve injury.

Excluded will be also all patients with contradictions for the use of Etoricoxib:
•Hypersensitivity to the active substance or to any of the excipients.
•Active peptic ulceration or active gastrointestinal (GI) bleeding.
•Patients who have experienced bronchospasm, acute rhinitis, nasal polyps, angioneurotic oedema, urticaria, or allergic-type reactions after taking acetyl-salicylic acid or NSAIDs including COX-2 (cyclooxygenase-2) inhibitors.
•Pregnancy and lactation
•Severe hepatic dysfunction (serum albumin <25 g/l or Child-Pugh score ≥10).
•Estimated renal creatinine clearance <30 ml/min.
•Inflammatory bowel disease.
•Congestive heart failure (NYHA II-IV).
•Patients with hypertension whose blood pressure is persistently elevated above 140/90mmHg and has not been adequately controlled
•Established ischemic heart disease, peripheral arterial disease, and/or cerebrovascular disease.
•Intake of one of the following drugs (current or in the last 3 days)
◦selective-serotonin-reuptake-inhibitor
◦cetoconazole
◦rifampicin
◦phenytoin
◦carbamazepine
◦dexamethasone or other systemic corticoids
◦traditional nonsteroidal antiphlogistics
◦cyclooxygenase-inhibitors
◦immunosuppressives
◦TNF-α-inhibitors
CONTACT: Christoph Maier, Dr. med +49/234/3026366 christoph.maier@rub.de 
University hospital Bergmannsheil department of pain therapy GERMANY
STUDY SPONSOR: Ruhr University of Bochum, GERMANY
 
** Transcranial Magnetic Stimulation (TMS) Effects on Pain Perception
The purpose of this study is to investigate the effects of transcranial magnetic stimulation on pain perception.


Chronic pain represents a huge public health concern and is generally poorly understood at a basic neurobiological level. Transcranial magnetic stimulation (TMS) is a non-invasive technique that uses electromagnetic pulses to temporarily stimulate specific brain areas in awake people (without the need for surgery, anesthesia, or other invasive procedures). Previous research suggests that TMS may be effective in reducing pain perception in healthy adults and in patients with various types of pain conditions, such as neuropathic pain. However, there is relatively little research on TMS and pain that addresses optimal TMS device parameters, optimal cortical targets, and potential differences in response to TMS between healthy persons and those with chronic pain.

The purpose of this trial is to study the effects of TMS on pain perception. Specifically, this study will determine optimal device parameters (dose) and brain targets for stimulation with TMS in order to reduce pain in patients with neuropathic pain and in healthy adults using laboratory pain methods.

Participants with Neuropathic Pain:
After an initial screening, eligible participants with neuropathic pain will receive a magnetic resonance imaging (MRI) scan to help determine the best target for TMS stimulation later in the study. Participants will be asked to record their pain experiences every day for 2-4 weeks before receiving the first of 2 laboratory pain assessments. The laboratory pain assessment uses a small device, controlled by a computer and attached to the underside of the forearm, to produce different temperature stimulations. As the device reaches a level considered painful to the participant, he/she can push a button to return to a level of comfort.

The next part of the trial involves two, 20-minute TMS treatment sessions per day for 5-days. Participants will be randomly assigned to one of two groups. Group A will receive real TMS and Group B will receive "sham" TMS. Study participation time for individuals with TGN is about 8 weeks, including about 10 hours (7 visits) at the Medical University of South Carolina (MUSC).

Healthy Volunteers:
In addition to an interview with researchers regarding medical history, healthy participants will complete a self-report screening to assess pain history and level of depression and anxiety. Eligible participants will be given a laboratory pain assessment, and be randomly assigned to one of two groups: group A will receive real TMS and group B will receive "sham" TMS. After TMS, participants will receive another full laboratory pain assessment and complete questionnaires. For healthy volunteers, participation in the study will take about 3 hours and may be completed in one or two visits.

INCLUSION CRITERIA:
For Healthy Adults:
•Between age of 21 and 60
•No prescription medications in previous 3 months
•No seizure history
•No depression
•Not suicidal
•No anxiety
•No hospitalizations or surgeries in previous 6 months
•No history of chronic pain conditions
•No implanted metal devices (e.g., pacemakers, metal plates, wires)
•Not pregnant
•No alcohol abuse/dependence history in previous 6 months
•No illicit drug use in previous 6 months
•Capable of reading, writing, giving consent, following instructions
•No history of brain surgery or history of loss of consciousness >15 minutes
•No history of autoimmune or endocrine disorder
•No significant anxiety about entering MRI scanner

For Patients with neuropathic pain:
•Between age of 21 and 75
•No seizure history
•Not taking medications shown to increase seizure risk (6 months)
•Not suicidal
•No hospitalizations or surgeries in previous 3 months
•No implanted metal devices (e.g., pacemakers, metal plates, wires)
•Not pregnant
•No alcohol abuse/dependence history in previous 6 months
•No illicit drug use in previous 6 months
•Capable of reading, writing, giving consent, following instructions
•Chronic pain (>6 months), not significantly relieved by pharmacological treatment
•No significant anxiety about entering MRI scanner
CONTACT: Contact: Jeffrey J. Borckardt, Ph.D. (843)867-5142 borckard@musc.edu
Associate Professor, Department of Psychiatry and Behavioral sciences Department of Anesthesiology and Perioperative Medicine, Medical University of South Carolina
STUDY SPONSOR: Medical University of South Carolina
COLLABORATORS: National Institute of Neurological Disorders and Stroke (NINDS)
 
** Effects of Vaporized Marijuana on Neuropathic Pain
The specific aim of this study is to measure the pain-relieving effects of vaporized marijuana in subjects with neuropathic pain. An evaluation of pain relief with mood, cognitive impairment, and psychomotor performance will also be collected to help evaluate the utility of vaporized marijuana in a neuropathic pain population.


The case for marijuana's medical use for pain is primarily from experimental studies with normal subjects, which have yielded conflicting results. Experimental subjects have been shown to have significant dose-dependant antinociception effect that is not reversed by opioid antagonism. In contrast to this positive antinociceptive effect, other experiments demonstrated hyperalgesic activity and probably enhancement of the perception of pain upon acute exposure in chronic users of marijuana.

In addition to studying spontaneous pain antinociception, it would be useful to evaluate the response to marijuana following evoked pain. Such evoked pain is produced by stimulation of the skin that is normally not noxious.

Because of the potential side effects of marijuana administration, one of the aims of the present study is to analyze inter-individual variability and the occurrence of dose-dependant analgesia of marijuana with an eye on defining tolerable dosing in clinical neuropathic pain syndromes.

Comparisons: Neuropathic and experimentally induced pain scores will be compared after the administration of escalating doses of low, high, and placebo marijuana cigarettes as provided by the National Institutes on Drug Abuse (NIDA).

CONDITIONS:
•Neuropathic Pain

•Reflex Sympathetic Dystrophy
•Peripheral Neuropathy
•Post-herpetic Neuralgia
•Post Stroke Pain
•Spinal Cord Injury
•Multiple Sclerosis

RELATED PUBLICATIONS: A randomized, placebo-controlled, crossover trial of cannabis cigarettes in neuropathic pain.
Wilsey B, Marcotte T, Tsodikov A, Millman J, Bentley H, Gouaux B, Fishman S.

ELIGIBILITY:
Inclusion Criteria:

•Age greater than 18 and less than 70
•Visual Analogue Scale (VAS pain intensity) greater than 3/10
•A negative urine drug screening test, i.e., no evidence of IV drug abuse
•Neuropathic pain due to reflex sympathetic dystrophy, peripheral neuropathy, post-herpetic neuralgia, post-stroke pain, multiple sclerosis or spinal cord injury

Exclusion Criteria:
•Presence of another painful condition of greater severity than the neuropathic pain condition which is being studied.
•Subjects with moderate-severe major depression, bipolar/mania, bipolar II/hypomania and schizophrenia or schizoaffective disorder.
•Unstable Type 1 or 2 diabetes defined as blood glucose more than 156 mg/dl
•History of traumatic brain injury
•Uncontrolled medical condition, including coronary artery disease, hypertension, cerebrovascular disease, asthma, tuberculosis (TB), chronic obstructive pulmonary disease (COPD), opportunistic infection, malignancy requiring active treatment, active substance abuse (alcohol or injection drugs).
•Current use of marijuana (e.g., within 30 days of randomization)
•Pregnancy as ascertained by a self-report and a mandatory commercial pregnancy test.
CONTACT: Haylee E. Donaghe, MS 916-734-2935 hedonaghe@ucdavis.edu
Responsible Party:  Barth L. Wilsey, MD, Univeristy of California, Davis

Study Sponsor: University of California, Davis
Collaborators:
•Center for Medicinal Cannabis Research
•VA Northern California Health Care System
Principal Investigator: Barth L Wilsey, MD University of California, Davis