Pharmacological and non-pharmacological treatments for neuropathic pain: Systematic review and French recommendations.

Background To evaluate the efficacy of gabapentin at 20 mg/kg per day in the treatment of vincristine-related neuropathic pain. Procedure Children aged 1-18 years who developed vincristine-induced neuropathy on a St Jude frontline acute lymphoblastic leukemia trial were prospectively enrolled on a randomized, double-blind, placebo-controlled, phase II trial with two treatment arms: gabapentin plus opioid versus placebo plus opioid. Daily evaluations of morphine dose (mg/kg per day) and pain scores were conducted for up to 21 days; the values of the two arms were compared to assess analgesic efficacy. Results Of 51 study participants, 49 were eligible for analyses. Twenty-five participants were treated with gabapentin, with a mean (SD) dose of 17.97 (2.76) mg/kg per day (median 18.26, range 6.82-21.37). The mean (SD) opioid doses taken, expressed as morphine equivalent daily (mg/kg per day), were 0.26 (0.43) in the gabapentin group (25 patients, 432 days) and 0.15 (0.22) in the placebo group (24 patients, 411 days; P = .15). Only the risk classification of acute lymphoblastic leukemia was significantly associated with the daily morphine dosage (P = .0178): patients in the lower risk arm received higher daily morphine dosages. Multivariate analyses revealed a significant difference between the groups' average daily scores for the previous 24 h and "right now." Conclusion In this population of children with vincristine-related neuropathic pain, opioid consumption and pain scores were higher in the gabapentin group than in the placebo group. Future randomized, double-blind, placebo-controlled studies should test gabapentin given longer or at a higher dose.

Prospective randomized trial of interventions for vincristine-related neuropathic pain.

Background In cancer patients, cancer pain is the most common cancer complication. About 60–90% of patients with advanced stage cancer experience various levels of pain, and about 30% of patients have been suffering from persistent severe pain. Bones are the most frequent targets of metastases in patients with cancer such as breast, prostate, lung, kidney, and thyroid. In advanced prostate cancer, bone metastasis leads to bone pain, skeletal fracture, and increased mortality. At least 75% of patients with bone metastasis experience bone pain. Case description We report three cases of cancer pain, treated with primary cancer from the prostate metastasis to the spine. All three patients had lower back pain that radiated to the left and right limbs, with mixed pain and bone pain, where early hospital admission shows the Numeric Rating Scale (NRS) pain scale 9–10. Treated with administration of adjuvant therapy (Gabapentin) and weak opioids (injections of Tramadol) as well as injections of Metylprednisolone (for 3 days), the patient's pain scale was evaluated, and the average NRS obtained on days 2–4 was 5–6. On day 5–8, treatment continued with Gabapentin and Tramadol injections, and the pain scale (NRS) decreased to 2–3. All patients on the 8-9th day of treatment also received Biphosphonates to reduce pain, bone damage, fracture risk, and blood calcium levels. Patients can be discharged with an oral Gabapentin prescription only. Conclusion A pain scale (NRS) reduction of >50% is obtained from the initial pain scale in cancer pain patients treated using a combination of adjuvant therapy and weak opioids.

Management of cancer pain with analgetic adjuvant and weak opioid in prostate cancer bone metastases: A case series.

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Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial)

Aim: The molecular mechanism of gabapentin (GBP)–morphine combinational function and its neuro-anatomical sites of action to prevent, to neutralize morphine side effects and also the enhancement its analgesic effect of morphine is unknown. Methods: Morphine (10 mg/kg), saline, co-injection: GBP (150 mg/kg) with morphine (10 mg/kg) were injected by intraperitoneal injection in rats under deep anaesthesia. C-Fos immunohistochemistry technique was used to locate c-Fos expression in rat hypothalamus. Results: Gabapentin in combination with morphine significantly (p < 0.01) attenuated the acute morphine induced c-Fos immunoreactive neuron in hypothalamus. Conclusion: GBP neutralized the morphine sensitization in rat hypothalamus. GBP might neuromodulate and or antagonize the receptor regulatory machinery of morphine sensitization circuit which might work for drug discovery of morphine abuse.

Gabapentin completely neutralized the acute morphine activation in the rat hypothalamus: a c-Fos study

Following publication of the original article [1], we have been notified that the tagging of one of the author names was done incorrectly in the XML version of the paper. Original and corrected tagging can be seen below.

/pdf/gabapentin-as-add-on-to-morphine-for-severe-neuropathic-or-z04vf1spam.pdf

Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial

Introduction Gabapentin is currently used ‘off-label’ in children and adolescents with chronic neuropathic pain, and reliable evidence of its effects and optimal dosing are lacking. Objectives The GABA-1 trial aims to compare the efficacy and safety of gabapentin liquid formulation relative to tramadol and to explore the pharmacokinetics of both drugs in the treatment of chronic, neuropathic or mixed pain in the paediatric population. Methods and analysis The trial is a multicentre, double-blind, double-dummy, randomised, active-controlled, non-inferiority trial. Participants aged from 3 months to Ethics and dissemination Ethic approval was obtained in the eight participating countries. Results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. Trial registration numbers 2014-004851-30 and NCT02722603. Trial status Ongoing research study, currently recruiting.

https://bmjopen.bmj.com/content/bmjopen/9/2/e023296.full.pdf

Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial—a study protocol

Rebecca Lundin

Papers

Gabapentin as add-on to morphine for severe neuropathic or mixed pain in children from age 3 months to 18 years - evaluation of the safety, pharmacokinetics, and efficacy of a new gabapentin liquid formulation: study protocol for a randomized controlled trial

Non-inferiority double-blind randomised controlled trial comparing gabapentin versus tramadol for the treatment of chronic neuropathic or mixed pain in children and adolescents: the GABA-1 trial—a study protocol