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Biomedical subjects

Michael C Rowbotham

Publications and source records attributed to Michael C Rowbotham.

At least 19 recordsLinked to original sources
PubMed2007

Recommendations for the management of herpes zoster.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

2-Aminopurine↗
PubMed2006

Placebo-controlled comparison of a morphine/dextromethorphan combination with morphine on experimental pain and hyperalgesia in healthy volunteers.

UNLABELLED: In this double-blind, placebo-controlled, crossover study we compared the analgesic effect of a single oral dose of 30-mg dextromethorphan and 30-mg morphine combination (MS/DM) to 30 mg morphine (MS) alone and either placebo or 30 mg dextromethorphan (DM) on cutaneous sensitization induced by heat/capsaicin (topical) sensitization on the forearm and the brief thermal sensitization model on the thigh in 22 healthy volunteers. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation in both sensitization models and the painfulness of acute thermal noxious stimulation on the upper arm. Compared with placebo, both MS/DM and morphine had some effect on the secondary hyperalgesia and reduced the painfulness of a noxious thermal stimulus. The analgesic effect of MS/DM was not superior to that of morphine on any outcome measure. These results differ from preclinical studies with animal experimental pain models in which DM markedly potentiated the analgesic effects of opioids, but they are in accordance with recent clinical trials for chronic pain. PERSPECTIVE: Adding dextromethorphan to morphine (1:1 ratio) did not enhance analgesia on measures of experimental cutaneous sensitization and acute noxious thermal stimulation in healthy volunteers. The results differ from preclinical studies but agree with clinical trials. Human experimental models of pain and neuronal sensitization, which are responsive to oral opioids, allow efficient study of opioid combination analgesics and simplify the process for determining the optimal dose and/or dose ratio.

Adult↗
PubMed2006

Natural history of pain following herpes zoster.

In a longitudinal observational study of 94 patients (39 M:55 F, mean age 69) at elevated risk for developing post herpetic neuralgia (PHN), the natural history of pain during the first 6 months after herpes zoster (HZ) rash onset was determined. Pain severity and impact were rated using pain-VAS, SF-MPQ, and MPI. Applying a definition of PHN of average daily pain >0/100 on the pain VAS during the last 48 h, 30 subjects had PHN at 6 months. These 30 subjects reported more pain and a higher SF-MPQ score (p<0.01) at study inclusion than the 64 subjects whose pain completely resolved by 6 months. At 6 months, mean daily pain in the PHN group was 11/100 (95% CI 5,16) and only nine of these subjects were still taking prescription medication for HZ pain. The rate of recovery (pain severity over time) was the same in the PHN and no-pain groups. At study inclusion, the SF-MPQ and MPI scores in our PHN group were similar to historical controls with chronic severe PHN enrolled in clinical trials, but by 6 months the scores in our PHN subjects were significantly lower than historic controls. Only two subjects met the more stringent criteria for 'clinically meaningful' PHN at 6 months (> or = 30/100 on the pain VAS). Defining PHN as average daily pain >0/100 at 6 months after rash onset appears to substantially overestimate the number of HZ patients negatively impacted by ongoing pain and disability.

Aged↗
PubMed2006

Pharmacologic management of complex regional pain syndrome.

Few randomized controlled trials of oral pharmacotherapy have been performed in patients with complex regional pain syndrome (CRPS). The prevalence of CRPS is uncertain. Severe and advanced cases of CRPS are easily recognized but difficult to treat and constitute a minority compared with those who meet minimum criteria for the diagnosis. Unsettled disability or liability claims limit pharmaceutical industry interest in the disorder. Many studies are small or anecdotal, or are reported on only via posters at meetings. Targeting the process of bone resorption with bisphosphonate-type compounds such as calcitonin, clodronate, and alendronate has shown efficacy in three published randomized controlled trials. Intravenous phentolamine has been studied both alone and in comparison to intravenous regional blockade or stellate ganglion block. Steroids continue to be administered by multiple routes without large-scale placebo-controlled trials. Topical medications have received little attention. There has been considerable interest in the use of thalidomide and TNF-alpha blockers for CRPS, but no published controlled trials as of yet. Numerous other oral drugs, including muscle relaxants, benzodiazepines, antidepressants, anticonvulsants, and opioids, have been reported on anecdotally. Some therapies have been the subject of early controlled studies, without subsequent follow-up (eg, ketanserin) or without an analogous well-tolerated and equally effective oral treatment (eg, intravenous ketamine). Gabapentin, tricyclic antidepressants, and opioids have been proven effective for chronic pain in disorders other than CRPS. Each has shown a broad enough spectrum of analgesic activity to be cautiously recommended for treatment of CRPS until adequate randomized controlled trials settle the issue. The relative benefit of oral medications compared with the widely used treatments of intensive physical therapy, nerve blocks, sympathectomy, intraspinally administered drugs, and neuromodulatory therapies (eg, spinal cord stimulation) remains uncertain. In summary, treatment of CRPS has received insufficient study and remains largely empirical.

Adrenergic Agents↗
PubMed2005

Mechanisms of neuropathic pain and their implications for the design of clinical trials.

A mechanism-based approach to treatment is alluring, but numerous practical problems impede its implementation. Although many new therapies have entered clinical trials, and randomized controlled trials have become larger and more sophisticated, pre-trial testing of underlying pain mechanisms is almost never performed for reasons of cost, risk to subjects, time required, and validation of the techniques used. Most registration clinical trials are performed in patients with post-herpetic neuralgia and painful diabetic neuropathy, but without more information on pain mechanisms, it remains uncertain how fully results in those two disorders can be generalized to patients with other types of chronic neuropathic pain. Examples of study designs and potential solutions are presented.

Analgesics↗
PubMed2005

Pregabalin for the treatment of fibromyalgia syndrome: results of a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: Fibromyalgia syndrome (FMS) is characterized by widespread musculoskeletal pain and lowered pain threshold. Other prominent symptoms include disordered sleep and fatigue. FMS affects an estimated 2% of the population, predominantly women. This trial was designed to evaluate the efficacy and safety of pregabalin, a novel alpha(2)-delta ligand, for treatment of symptoms associated with FMS. METHODS: This multicenter, double-blind, 8-week, randomized clinical trial compared the effects of placebo with those of 150, 300, and 450 mg/day pregabalin on pain, sleep, fatigue, and health-related quality of life in 529 patients with FMS. The primary outcome variable was the comparison of end point mean pain scores, derived from daily diary ratings of pain intensity, between each of the pregabalin treatment groups and the placebo group. RESULTS: Pregabalin at 450 mg/day significantly reduced the average severity of pain in the primary analysis compared with placebo (-0.93 on a 0-10 scale) (P </= 0.001), and significantly more patients in this group had >/=50% improvement in pain at the end point (29%, versus 13% in the placebo group; P = 0.003). Pregabalin at 300 and 450 mg/day was associated with significant improvements in sleep quality, fatigue, and global measures of change. Pregabalin at 450 mg/day improved several domains of health-related quality of life. Dizziness and somnolence were the most frequent adverse events. Rates of discontinuation due to adverse events were similar across all 4 treatment groups. CONCLUSION: Pregabalin at 450 mg/day was efficacious for the treatment of FMS, reducing symptoms of pain, disturbed sleep, and fatigue compared with placebo. Pregabalin was well tolerated and improved global measures and health-related quality of life.

Adult↗
PubMed2005

Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial.

UNLABELLED: In 47 patients with postherpetic neuralgia (PHN) who had never had an adequate trial of any antidepressant, we performed a randomized, double-blind, parallel design trial comparing desipramine, amitriptyline, and fluoxetine. Patients were titrated to a maximum of 150 mg/day for desipramine and amitriptyline and 60 mg/day for fluoxetine over a 3-week period and then treated for an additional 3 weeks before tapering off study medication. A total of 38 subjects (81%) completed the entire trial. The modified intent-to-treat analysis of percent change in daily diary pain intensity scores showed no significant differences among the 3 drugs (ANOVA P = .120). Desipramine produced the greatest reduction in pain intensity (47%), followed by amitriptyline (38%) and fluoxetine (35%). Clinically meaningful pain relief (moderate or better) was significantly more likely with desipramine (12/15 patients) than with amitriptyline (9/17) or fluoxetine (5/15); chi(2)P = 0.036). The 11 subjects using opioids at study entry had smaller reductions in pain than those not using concomitant opioids. The fluoxetine group had the highest noncompletion rate (33%), with 1 subject hospitalized for hyponatremia. Although the magnitude of pain reduction and the category pain relief rating was not significantly different among the 3 drugs, the tricyclics desipramine and amitriptyline were well tolerated and provided clinically meaningful pain relief in 53% to 80% of subjects. PERSPECTIVE: Few clinical trials focus on patients who are naïve to an entire class of medication. In this randomized blinded trial, the tricyclic antidepressants desipramine and amitriptyline were compared to the serotonin-selective antidepressant fluoxetine. All 3 drugs reduced PHN pain, with desipramine providing satisfactory relief in 80% of those treated.

Adult↗
PubMed2005

Is fibromyalgia a neuropathic pain syndrome?

The fibromyalgia syndrome (FM) seems an unlikely candidate for classification as a neuropathic pain. The disorder is diagnosed based on a compatible history and the presence of multiple areas of musculoskeletal tenderness. A consistent pathology in either the peripheral or central nervous system (CNS) has not been demonstrated in patients with FM, and they are not at higher risk for diseases of the CNS such as multiple sclerosis or of the peripheral nervous system such as peripheral neuropathy. A large proportion of FM sufferers have accompanying symptoms and signs of uncertain etiology, such as chronic fatigue, sleep disturbance, and bowel/bladder irritability. With the exception of migraine headaches and possibly irritable bowel syndrome, the accompanying disorders are clearly not neurological in origin. The impetus to classify the FM as a neuropathic pain comes from multiple lines of research suggesting widespread pain and tenderness are associated with chronic sensitization of the CNS. An examination of how the term neuropathic pain is defined reveals a conceptual split into 2 partially overlapping groups of disorders: those with demonstrable pathology in the nervous system and those characterized primarily by enduring dysfunction in the nervous system. Requiring demonstrable pathology in the nervous system in the definition of neuropathic pain is the traditional approach. The expansion of the definition to require only enduring nervous system dysfunction is less palatable because it opens the classification to many disorders of uncertain etiology, including complex regional pain syndrome. As it is uncertain which of the many different chronic pain syndromes include an enduring component of central sensitization, restricting the term "neuropathic pain" to those disorders with a primary etiology clearly related to the peripheral or CNS is prudent and consistent with clinical practice.

Fibromyalgia↗
PubMed2004

Complex regional pain syndrome-like symptoms during herpes zoster.

Complex Regional Pain Syndrome (CRPS) associated with herpes zoster (HZ) was first reported by Sudeck in 1901 (Sudeck, 1901) and is recognized clinically. However, only 13 cases have been published in the literature, and nothing is known about the incidence, prevalence, or natural history (Chester, 1992; Foster et al., 1989; Grosslight et al., 1986; Ketz and Schliack,1968; Kishimoto et al., 1995; Querol and Cisneros, 2001; Sudeck, 1901; Visitsunthorn and Prete, 1981). The aim of the present study was to determine the prevalence of CRPS-like symptoms in a prospectively gathered cohort of subjects with HZ and to follow the natural history of their pain and sensory disturbance during the first 6 months after onset of HZ. Subjects were evaluated at four time points after HZ: 2-6 weeks, 6-8 weeks, 3 months, and 6 months. Only subjects aged 50 or older with pain VAS ratings of >/=20/100 at 2-6 weeks were eligible. The first (screening) visit included a neurological and physical examination that was updated at each subsequent visit. Assessments included ratings of pain intensity, allodynia severity, and rash severity. The neurological exam included determination of presence or absence of the following CRPS-like symptoms: (1) increased sweating, (2) color changes, (3) skin temperature changes, (4) weakness of the affected area based on physical exam, (5) edema, and (6) extension of CRPS-like symptoms outside the affected dermatome. For subjects with HZ in dermatomes that can include the limbs (C4-T2 and L1-S2), extremity involvement was considered present if allodynia or rash extended beyond the neck of the humerus (upper extremity), the inguinal ligament (anterior lower extremity), or gluteal sulcus (posterior lower extremity). Involvement of the extremity was considered proximal if neither HZ rash nor allodynia extended past the elbow (upper extremity) or knee (lower extremity). Of the first 75 subjects recruited, 25 had HZ outbreaks in dermatomes that extended into the extremities (C4-T2 and L1-S2). In this group, 8 subjects had no extremity involvement, 8 had proximal extremity involvement, and 9 had distal extremity involvement. Subjects with distal extremity HZ reported more pain across the four visits (p < 0.05). At 3 months, more subjects with distal extremity involvement met criteria for PHN (8 out of 9, 89%), while only 4 out of 8 (50%) with proximal involvement and 2 out of 8 (25%) of subjects without extremity involvement met criteria for PHN (Chi-square test: p < 0.05). Only 25 out of the remaining 50 (50%) subjects with outbreaks in dermatomes that do not include the extremities met criteria for PHN at 3 months (Chi-square test: p < 0.05). Six months after onset of HZ, 6 out of 9 subjects with distal extremity involvement met PHN criteria compared with 2 out of 8 (25%) with proximal involvement and 2 out of 8 (25%) without extremity involvement (Chi-square test: p = 0.12). Fifteen out of 50 (30%) subjects with outbreaks in dermatomes that do not include the extremities met criteria for PHN (Chi-square test: p < 0.05). No subject had all six CRPS-like symptoms. Of the 17 subjects with extremity involvement, 9 subjects had '0-2 CRPS-like symptoms' and 8 had '3-5 CRPS-like symptoms'. None of the eight subjects without extremity involvement had any CRPS-like symptoms. Of the 50 subjects with HZ outside the extremity, only one had abdominal weakness. Pain ratings were higher in subjects with '3-5 CRPS-like symptoms'. More subjects with '3-5 CRPS-like symptoms' met criteria for PHN at 3 months (7 out of 8, 88%), compared to 5 out of 9 (55%) of subjects with '0-2 CRPS-like symptoms' (p = 0.07). At 6 months, 2 out of 9 (22%) of subjects with '0-2 CRPS-like symptoms' met criteria for PHN, compared with 6 out of 8 (75%) of subjects with '3-5 CRPS-like symptoms' (Chi-square test: p < 0.03). Two case-reports are presented. In summary, the occurrence of CRPS-like symptoms is common in subjects with HZ outbreaks affecting the extremity, particularly if the distal extremity is involved. It is uncertain if the pathophysiology underlying the CRPS-like symptoms observed in this study is similar to that of CRPS from other causes, or if it is relatively specific to HZ. Development of PHN is common in subjects who have experienced CRPS-like symptoms. More aggressive preventive treatments may be justified in this high-risk subset of HZ subjects to prevent development of PHN. Prospective randomized controlled studies are needed to determine which subjects are most likely to benefit and when treatment should begin.

Aged↗
PubMed2004

Venlafaxine extended release in the treatment of painful diabetic neuropathy: a double-blind, placebo-controlled study.

To evaluate the efficacy and safety of 6 weeks of venlafaxine extended-release (ER) (75 mg and 150-225 mg) treatment in patients with painful diabetic neuropathy. This multicenter, double-blind, randomized, placebo-controlled study included 244 adult outpatients with metabolically stable type 1 or 2 diabetes with painful diabetic neuropathy. Primary efficacy measures were scores on the daily 100 mm Visual Analog Pain Intensity (VAS-PI) and Pain Relief (VAS-PR) scales. Secondary efficacy measures included the Clinical Global Impressions-Severity of Illness and the Clinical Global Impressions-Improvement, Patient Global Rating of Pain Relief, and percentage of patients achieving 50% reduction in pain intensity. Baseline pain intensity was 68.7 mm (moderately severe). At week 6, the percentage reduction from baseline in VAS-PI was 27% (placebo), 32% (75 mg), and 50% (150-225 mg; P < 0.001 vs placebo). Mean VAS-PR scores in the 150-225 mg group were significantly greater than placebo at week 6 (44 vs 60 mm; P < 0.001). The number needed to treat (NNT) for 50% pain intensity reduction with venlafaxine ER 150-225 mg was 4.5 at week 6. Nausea and somnolence were the most common treatment-emergent adverse events. Seven patients on venlafaxine had clinically important ECG changes during treatment. Venlafaxine ER appears effective and safe in relieving pain associated with diabetic neuropathy. NNT values for higher dose venlafaxine ER are comparable to those of tricyclic antidepressants and the anticonvulsant gabapentin.

Aged↗
PubMed2003

Oral opioid therapy for chronic peripheral and central neuropathic pain.

BACKGROUND: Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied. METHODS: Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent mu-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels. RESULTS: Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit. CONCLUSIONS: The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.

Adult↗
PubMed2003

Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations.

Chronic neuropathic pain, caused by lesions in the peripheral or central nervous system, comes in many forms. We describe current approaches to the diagnosis and assessment of neuropathic pain and discuss the results of recent research on its pathophysiologic mechanisms. Randomized controlled clinical trials of gabapentin, the 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants provide an evidence-based approach to the treatment of neuropathic pain, and specific recommendations are presented for use of these medications. Continued progress in basic and clinical research on the pathophysiologic mechanisms of neuropathic pain may make it possible to predict effective treatments for individual patients by application of a pain mechanism-based approach.

Analgesics↗
PubMed2003

A randomized study of the effect of oral lamotrigine and hydromorphone on pain and hyperalgesia following heat/capsaicin sensitization.

In this randomized double-blind placebo-controlled study, the analgesic effect of oral lamotrigine (400 mg) on cutaneous sensitization induced with the heat/capsaicin sensitization model was compared with the effect of oral hydromorphone (8 mg) in healthy volunteers. In a separate session, intravenous remifentanil (0.10 microg.kg(-1).min(-1)) and placebo were administered. This session was used as an additional reference comparator. Outcome measures were the areas of secondary hyperalgesia to brush and von Frey hair stimulation and the painfulness of noxious thermal stimulation in nonsensitized skin. Compared with placebo, both intravenous remifentanil and oral hydromorphone significantly suppressed secondary hyperalgesia and acute thermal nociception. Oral lamotrigine did not reduce secondary hyperalgesia or acute thermal nociception but produced side effects of severity comparable with that of oral hydromorphone. Although lamotrigine is efficacious in the management of some types of chronic neuropathic pain, the lack of effect of this agent on human experimental pain suggests that its analgesic effects depend on nerve injury-associated abnormalities, which cannot be simulated in healthy human volunteers.

Adult↗
PubMed2002

Relief of post-herpetic neuralgia by surgical removal of painful skin.

We present a case of longstanding PHN treated by skin excision of the area of greatest pain (11.3 x 26.0 cm(2)). The operation reduced pain, eliminated tactile allodynia, and facilitated greatly reduced medication use over a 1-year follow-up period. Fourteen punch biopsies and 10 strips of skin (each 10 mm long) from the excised painful PHN skin were qualitatively assessed by double-label immunofluorescence using antibodies against protein-gene-product 9.5 (PGP9.5), 200 kDa neurofilament protein (NF), calcitonin gene-related peptide (CGRP) and vanilloid receptor-1 (VR-1). Compared with a punch biopsy from mirror image skin, the pattern of cutaneous innervation in PHN skin was consistently and substantially different. The results may explain the anatomical basis of the capsaicin-response test and have implications for our understanding of clinical mechanisms underlying PHN pain.

Aged↗