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Ian Gilron

Publications and source records attributed to Ian Gilron.

16 recordsLinked to original sources
PubMed2026

Assessment of blinding in pharmacotherapy and noninvasive neuromodulation randomized controlled trials for neuropathic pain in adults.

In randomized controlled trials (RCTs), study participants and research personnel are often blinded to minimize biases related to knowing treatment allocation. To determine if blinding was effective, participants may be asked which treatment they believe they received ("treatment guess"). This descriptive review characterized blinding assessment (BA) reporting in pharmacotherapy and neuromodulation neuropathic pain RCTs. Of 288 papers, 36 (12.5%) reported a BA. One paper reported the results of 2 studies, so in total 37 studies with a BA were assessed. Of these, 19 were crossover, 17 parallel, and 1 partial crossover in design. All 37 studies assessed participant blinding, and 10 also assessed investigator blinding. Approximately 27% included an "unsure" answer option for treatment guess, and 38% asked the reason for the guess. There were no clear patterns in BA reporting across time nor based on treatment type. Seventeen trials provided sufficient data to calculate Bang Blinding Index (BI) to determine blinding success. Participants remained blinded (BI = 0 &#xb1; 0.2) in 10/17 placebo and 10/17 treatment arms, 6 placebo and 5 treatment arms had a BI > 0.2 suggesting possible unblinding, whereas 1 placebo and 2 treatment arms had a BI < -0.2 suggesting misinformed guessing. Overall, we found that BAs are done in a minority of published neuropathic pain trials and with variable methodology. Given the importance of minimizing risk of bias because of treatment unblinding, future studies should consider including BAs, and further consensus building is necessary to determine if and how BAs should be conducted and interpreted in analgesic clinical trials.

Bias↗
PubMed2006

Neuropathic pain: a practical guide for the clinician.

Neuropathic pain, caused by various central and peripheral nerve disorders, is especially problematic because of its severity, chronicity and resistance to simple analgesics. The condition affects 2%-3% of the population, is costly to the health care system and is personally devastating to the people who experience it. The diagnosis of neuropathic pain is based primarily on history (e.g., underlying disorder and distinct pain qualities) and the findings on physical examination (e.g., pattern of sensory disturbance); however, several tests may sometimes be helpful. Important pathophysiologic mechanisms include sodium-and calcium-channel upregulation, spinal hyperexcitability, descending facilitation and aberrant sympathetic-somatic nervous system interactions. Treatments are generally palliative and include conservative nonpharmacologic therapies, drugs and more invasive interventions (e.g., spinal cord stimulation). Individualizing treatment requires consideration of the functional impact of the neuropathic pain (e.g., depression, disability) as well as ongoing evaluation, patient education, reassurance and specialty referral. We propose a primary care algorithm for treatments with the most favourable risk-benefit profile, including topical lidocaine, gabapentin, pregabalin, tricyclic antidepressants, mixed serotonin-norepinephrine reuptake inhibitors, tramadol and opioids. The field of neuropathic pain research and treatment is in the early stages of development, with many unmet goals. In coming years, several advances are expected in the basic and clinical sciences of neuropathic pain, which will provide new and improved therapies for patients who continue to experience this disabling condition.

Algorithms↗
PubMed2006

Review article: the role of anticonvulsant drugs in postoperative pain management: a bench-to-bedside perspective.

PURPOSE: Anticonvulsant drugs are effective in the treatment of chronic neuropathic pain but were not, until recently, thought to be useful in more acute conditions such as postoperative pain. However, similar to nerve injury, surgical tissue injury is known to produce neuroplastic changes leading to spinal sensitization and the expression of stimulus-evoked hyperalgesia and allodynia. Pharmacological effects of anticonvulsant drugs which may be important in the modulation of these postoperative neural changes include suppression of sodium channel, calcium channel and glutamate receptor activity at peripheral, spinal and supraspinal sites. The purpose of this article is to review preclinical evidence and clinical trial data describing the efficacy and safety of anticonvulsant drugs in the setting of postoperative pain management. SOURCE: A Medline search was performed to retrieve available literature on the basic and clinical pharmacology of anticonvulsant drugs as they pertain to postoperative pain management. PRINCIPAL FINDINGS: Numerous laboratory studies have described analgesic effects of different anticonvulsant drugs in experimental pain models. Furthermore, several recent clinical trials have shown that anticonvulsants may reduce spontaneous and movement-evoked pain, as well as decrease opioid requirements postoperatively. Some early findings suggest further that anticonvulsant drugs may alleviate postoperative anxiety, accelerate postoperative functional recovery and reduce chronic postsurgical pain. CONCLUSION: Given the incomplete efficacy of currently available non-opioid analgesics, and the identified benefits of opioid sparing, anticonvulsant medications may be useful adjuncts for postoperative analgesia. Further research in this field is warranted.

Analgesics↗
PubMed2006

The impact of therapy on quality of life and mood in neuropathic pain: what is the effect of pain reduction?

Mood and quality of life (QOL) outcomes vary widely in neuropathic pain trials. This may be a result of variable analgesia and other treatment effects. We evaluated the relationship between pain reduction and mood/QOL in neuropathic pain. Pain, side effects, QOL, and mood from a trial of morphine, gabapentin, and a morphine-gabapentin combination were examined. Baseline QOL was impaired according to Short Form Health Survey (SF-36) scores. Baseline mood, according to Profile of Mood States scores, was comparable to that of a nondepressed population. Pain reduction with all three active trial treatments correlated with improved QOL. Pain reduction with morphine and with gabapentin correlated with improved mood. Pain reduction with a morphine-gabapentin combination correlated with improvement in only one of several domains of the Profile of Mood States. Severity of sedation, constipation, and dry mouth during any treatment did not correlate with mood/QOL changes. These results can be interpreted to imply that larger analgesic treatment effect sizes lead to more substantial improvements in QOL and/or mood. However, other beneficial or adverse treatment-related side effects may also affect mood/QOL. Therefore, future studies are needed to also evaluate the impact of treatment-related side effects on mood/QOL in analgesic trials.

Affect↗
PubMed2005

Chronobiological characteristics of painful diabetic neuropathy and postherpetic neuralgia: diurnal pain variation and effects of analgesic therapy.

Clinical impressions suggest that neuropathic pain is often worse at night and significantly impairs sleep. However, the temporal pattern of neuropathic pain during waking hours has not been clearly characterized. Using clinical trial data, we have evaluated the diurnal variation of pain intensity before and during analgesic treatment in patients with diabetic neuropathy (DN) and postherpetic neuralgia (PHN). Pain intensity (0-10) measures throughout the day from a placebo-controlled trial of around-the-clock administration of gabapentin, morphine and a gabapentin-morphine combination in neuropathic pain patients were examined. Baseline data in untreated patients revealed no effect of day of week but a significant effect of time of day in both DN (P < 0.001) and PHN (P < 0.001) such that pain intensity progressively increases throughout the day. This temporal pattern is essentially preserved during treatment with gabapentin, morphine and their combination. Neuropathic pain intensity progressively increases throughout the day and this temporal profile appears to be unaffected by treatment with gabapentin and/or morphine. Advancing our understanding of the chronobiology of neuropathic pain may shed new light on various neurohormonal and neurophysiologic influences and lead to the identification of novel therapeutic targets. Furthermore, recognizing diurnal pain patterns may guide treatment strategies such as the targeted timing of analgesic therapies.

Adult↗
PubMed2005

Morphine, gabapentin, or their combination for neuropathic pain.

BACKGROUND: The available drugs to treat neuropathic pain have incomplete efficacy and dose-limiting adverse effects. We compared the efficacy of a combination of gabapentin and morphine with that of each as a single agent in patients with painful diabetic neuropathy or postherpetic neuralgia. METHODS: In this randomized, double-blind, active placebo-controlled, four-period crossover trial, patients received daily active placebo (lorazepam), sustained-release morphine, gabapentin, and a combination of gabapentin and morphine--each given orally for five weeks. The primary outcome measure was mean daily pain intensity in patients receiving a maximal tolerated dose; secondary outcomes included pain (rated according to the Short-Form McGill Pain Questionnaire), adverse effects, maximal tolerated doses, mood, and quality of life. RESULTS: Of 57 patients who underwent randomization (35 with diabetic neuropathy and 22 with postherpetic neuralgia), 41 completed the trial. Mean daily pain (on a scale from 0 to 10, with higher numbers indicating more severe pain) at a maximal tolerated dose of the study drug was as follows: 5.72 at baseline, 4.49 with placebo, 4.15 with gabapentin, 3.70 with morphine, and 3.06 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). Total scores on the Short-Form McGill Pain Questionnaire (on a scale from 0 to 45, with higher numbers indicating more severe pain) at a maximal tolerated dose were 14.4 with placebo, 10.7 with gabapentin, 10.7 with morphine, and 7.5 with the gabapentin-morphine combination (P<0.05 for the combination vs. placebo, gabapentin, and morphine). The maximal tolerated doses of morphine and gabapentin were lower (P<0.05) with the combination than for each drug as single agent. At the maximal tolerated dose, the gabapentin-morphine combination resulted in a higher frequency of constipation than gabapentin alone (P<0.05) and a higher frequency of dry mouth than morphine alone (P<0.05). CONCLUSIONS: Gabapentin and morphine combined achieved better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth as the most frequent adverse effects.

Adult↗
PubMed2005

A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement-evoked pain after abdominal hysterectomy.

Current treatments for post-injury movement-evoked pain are inadequate. Non-opioids may complement opioids, which preferentially reduce spontaneous pain, but most have incomplete efficacy as single agents. This trial evaluates efficacy of a gabapentin-rofecoxib combination following hysterectomy. In addition to IV-PCA morphine, 110 patients received either placebo, gabapentin (1800 mg/day), rofecoxib (50 mg/day) or a gabapentin-rofecoxib combination (1800/50 mg/day) starting 1 h pre-operatively for 72 h. Outcomes included pain at rest, evoked by sitting, peak expiration and cough, morphine consumption and peak expiratory flow (PEF). For placebo, gabapentin, rofecoxib and combination, 24 h pain (100 mm VAS) was: at rest-23.6 (P<0.05 vs. all treatments), 13.8, 14.4 and 12.1; during cough-50.7 (P<0.05 vs. all treatments), 41.5, 44.8 and 30.8; 48 h morphine consumption (mg) was: 130.4 (P<0.05 vs. all treatments), 81.7, 75.6 and 57.2 (P<0.05 vs. gabapentin and rofecoxib) and 48 h PEF (% baseline) was: 63.9 (P<0.05 vs. all treatments), 77.2, 76.7 and 87.5 (P<0.05 vs. gabapentin and rofecoxib). Adverse effects were similar in all groups except sedation which was more frequent with gabapentin. Combination and rofecoxib reduced pain interference with movement, mood and sleep (P<0.05) and combination was superior to gabapentin for all these three (P<0.05). These data suggest that a gabapentin-rofecoxib combination is superior to either single agent for postoperative pain. Other benefits include opioid sparing, reduced interference with movement, mood and sleep and increased PEF suggesting accelerated pulmonary recovery. Future research should identify optimal dose-ratios for this and other analgesic combinations.

Adult↗
PubMed2005

Combination pharmacotherapy for neuropathic pain: current evidence and future directions.

Current drugs reduce neuropathic pain and improve mood and quality of life. However, as single agents they are limited by incomplete efficacy and dose-limiting adverse effects. Recent experimental and clinical data support the potential of combination pharmacotherapy for neuropathic pain. Therapeutic benefits may include greater efficacy, lower doses and fewer adverse effects. Due to potential adverse, as well as beneficial, drug interactions, safety and efficacy of specific combinations must be empirically evaluated. Techniques such as isobolographic analysis, response-surface modeling and other model-free tests have been used in order to characterize analgesic interactions as antagonistic, additive or synergistic. Whether synergistic or not, a clinically useful combination could simply have additive or even subadditive analgesia, provided that there is less additivity for side effects. Despite widespread clinical use, there are surprisingly few published observations on combination therapy for neuropathic pain. This review discusses future directions and proposes research strategies aimed at bridging current knowledge gaps, including safety, compliance and cost-effectiveness; discovering optimal drug combinations and dose ratios; comparing concurrent with sequential combination therapy; and combining more than two drugs. Continued close integration of basic and clinical sciences is crucial in further harnessing the potential of combination pharmacotherapy in neuropathic pain.

Amines↗
PubMed2003

Trends in opioid use for chronic neuropathic pain: a survey of patients pursuing enrollment in clinical trials.

PURPOSE: Clinical trials suggest that opioids relieve neuropathic pain and decrease pain-related disability. We conducted a pilot study of current prescribing trends and patients' attitudes towards opioids for neuropathic pain. METHODS: A patient questionnaire was completed by individuals pursuing enrollment in neuropathic pain clinical trials at our facility. RESULTS: Of 154 patients with diabetic neuropathy (55.2%), postherpetic neuralgia (29.9%), idiopathic peripheral neuropathy (9.7%) and other neuropathies (5.2%), 73.4% complained of inadequate pain control, the mean pain duration was 4.7 (SD = 4.4) yr and the mean pain intensity (0-10) was 7.7 (SD = 2.3). In this group, 40.9% had never tried opioids and 24.7% had never tried any opioids, tricyclic antidepressants or anticonvulsants. Only 9.7% were receiving long-acting opioids or "around the clock" dosing whereas 25.3% were receiving opioids on an "as needed" basis. Opioids combined with tricyclic antidepressants and/or anticonvulsants were used in 11.0%. Fear of addiction and adverse effects were expressed by 31.8% and 46.8% respectively. CONCLUSION: These data suggest that barriers to opioid therapy for neuropathic pain include patients', and possibly physicians', fears of addiction and adverse effects, which are exaggerated in light of current evidence. The merits of continuous treatment with sustained-release opioids, "as needed" dosing with short-acting preparations, or combining opioids with other agents are discussed. Continued research and communication between health professionals, law enforcement officials and legislators is vital in order to facilitate appropriate opioid use which has a minimal negative impact on the public yet optimally benefits individuals who suffer from disabling neuropathic pain.

Analgesics, Opioid↗
PubMed2002

The relationship between movement-evoked versus spontaneous pain and peak expiratory flow after abdominal hysterectomy.

UNLABELLED: The pathogenesis of postoperative lung dysfunction implies a role for movement-evoked pain (e.g., splinting/hypoventilation because of pain avoidance). However, interactions between evoked pain and respiratory physiology are poorly understood. Thus, we examined the relationship between evoked versus spontaneous pain and one index of pulmonary function. In 25 patients having undergone a hysterectomy, visual analog scale ratings (100 mm) for spontaneous pain (REST) and pain during sitting (SIT), forced expiration (BLOW), and coughing (COUGH) were measured together with peak expiratory flow (PEF) at eight time points during postoperative Days 1 and 2. Secondary outcome measures included oxygen saturation and oxygen requirements. Pain was significantly correlated with PEF for COUGH, SIT, BLOW, and REST at eight, seven, four, and two of the eight studied time points, respectively. Mean visual analog scale scores [SE] for COUGH (26.1 mm [1.7]) and SIT (21.5 mm [1.5]) were greater (P < 0.05) than REST (10.5 mm [0.8]), and COUGH was greater (P < 0.05) than BLOW (16.8 mm [1.3]). All pain measures diminished (P < 0.05), and PEF reductions improved (P < 0.05) across the study period. We hypothesize that the consistent negative correlation of COUGH-evoked pain with PEF is, in part, caused by avoidance of coughing, which ultimately limits deep inspiration, lung reexpansion, and clearance of secretions. IMPLICATIONS: Movement-evoked pain may be an important contributor to postoperative complications, but its mechanisms are poorly understood. This study provides the first evidence that postoperative evoked pain correlates with lung function and highlights the need for future research on mechanisms and implications of this phenomenon.

Adult↗
PubMed2002

Dextromethorphan and memantine in painful diabetic neuropathy and postherpetic neuralgia: efficacy and dose-response trials.

BACKGROUND: There are few repeated dose-controlled trials of N-methyl-d-aspartate glutamate receptor antagonists in patients with neuropathic pain. The authors sought to evaluate two low-affinity N-methyl-d-aspartate antagonists using a novel two-stage design. METHODS: The authors studied patients with painful diabetic neuropathy (DN) and postherpetic neuralgia (PHN) in two crossover trials: (1) efficacy trial (dextromethorphan vs. memantine vs. active placebo [lorazepam]) and (2) dose-response trial of the preferred active drug in responders from the first study (0% vs. 25% vs. 50% vs. 100% of each patient's maximally tolerated dose). Pain intensity was measured on a 20-point scale. RESULTS: Nineteen of 23 DN patients and 17 of 21 PHN patients completed the efficacy trial. Median doses for DN and PHN were 400 and 400 mg/day dextromethorphan, 55 and 35 mg/day memantine, and 1.8 and 1.2 mg/day lorazepam. In the efficacy trial, among patients with DN, dextromethorphan reduced pain intensity by a mean of 33% from baseline, memantine reduced pain intensity by a mean of 17%, and lorazepam reduced pain intensity by a mean of 16%; the proportions of subjects achieving greater than moderate pain relief were 68% with dextromethorphan, 47% with memantine, and 37% with lorazepam. Mean reductions in pain intensity in patients with PHN were 6% with dextromethorphan, 2% with memantine, and 0% with lorazepam. No comparison with placebo reached statistical significance in the efficacy trial. In the 10 DN subjects who responded to dextromethorphan, there was a significant dose-response effect on pain intensity (P = 0.035), with the highest dose significantly better than that of lorazepam (P = 0.03). CONCLUSIONS: Dextromethorphan is effective in a dose-related fashion in selected patients with DN. This was not true of PHN, suggesting a difference in pain mechanisms. Selective approaches to pain-relevant N-methyl-d-aspartate receptors are warranted.

Adult↗
PubMed2002

Patients' attitudes and prior treatments in neuropathic pain: a pilot study.

BACKGROUND: Ongoing research continues to expand the knowledge of neuropathic pain. It is vital that established treatments and valuable discoveries ultimately improve patient care. OBJECTIVES: Attitudes and prior treatments of patients being screened for neuropathic pain trials were evaluated to provide further understanding of the barriers to the management of neuropathic pain. METHODS: A questionnaire was completed by patients with neuropathic pain who were either referred by local physicians or self referred in response to clinical trial advertisements from the authors' facility. RESULTS: In total, 151 patients completed the questionnaire. Diagnoses included diabetic neuropathy (55.6%), postherpetic neuralgia (29.8%), idiopathic peripheral neuropathy (9.3%) and others (5.3%). The mean pain duration was 4.7 years, and the mean daily pain (on a score of 0 to 10) was 7.6. During questioning, 72.8% complained of inadequate pain control and 25.2% had never tried any antineuropathic analgesics (tricyclic antidepressants, opioids or anticonvulsants). New antineuropathic analgesics (eg, gabapentin) were being used by only 16.6%. Opioids, tricyclic antidepressants and anticonvulsants had never been tried by 41.1%, 59.6% and 72.2%, respectively. Fears of addiction and adverse effects were expressed by 31.8% and 48.3%, respectively. CONCLUSIONS: New, and even conventional, therapies are often not pursued, despite inadequate pain control. Several issues are discussed, including patient barriers to seeking pain management, patient and physician barriers to analgesic drug therapy, and appropriate use of and access to multidisciplinary pain centres. Failure to implement therapeutic advances in pain management not only hinders improvement in patient care, but also may render futile decades of research. Widespread professional, patient and public education, as well as continued interdisciplinary research on treatment barriers, is essential.

Aged↗