Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine

Arai, Young‐Chang P.; Matsubara, Takako; Shimo, Kazuhiro; Suetomi, Katsutoshi; Nishihara, Makoto; Ushida, Takahiro; Kobayashi, Kunio; Suzuki, Chise; Kinoshita, Akiko; Kondo, Miki; Matsubara, Satuki; Hayashi, Ruiko; Tohyama, Yukio; Nishida, Kikuyo; Arakawa, Maki

doi:10.1007/s00540-010-0913-6

Cited by 42 publications

(35 citation statements)

References 19 publications

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“…In the context of neuropathic cancer pain, there is strong evidence from randomized controlled trials that the addition of gabapentin improves analgesia provided by opioid monotherapy; furthermore, treatment‐related side effects are significantly less frequent with dual opioid and gabapentin therapy . Similarly, the addition of both gabapentin and a tricyclic antidepressant to an opioid regimen was found to effectively manage neuropathic cancer pain by decreasing the total pain score and the paroxysmal pain episodes . Comparative efficacy of amitriptyline and gabapentinoids was demonstrated in a randomized placebo‐controlled study in neuropathic cancer pain .…”

Section: Discussionmentioning

confidence: 99%

Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population

Anghelescu

Steen

et al. 2016

Pediatric Blood & Cancer

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Background Neuropathic pain (NP) after definitive surgery for extremity osteosarcoma (OS) has not been previously characterized. This study prospectively investigates the incidence, duration, and treatment of NP in limb sparing surgery and amputation groups. Procedure In patients treated for OS on a chemotherapy and definitive surgery (limb sparing vs. amputation) protocol (OS08), we prospectively collected the following data: (i) demographical data (age, sex, race); (ii) NP time of onset and duration; and (iii) dose (starting, maximum) and duration of gabapentin, amitriptyline, and methadone treatment. Results Thirty-seven patients underwent 38 definitive surgeries: limb sparing (26, 68.4%) or amputations (12, 31.6%). Localization included lower extremity (30, 81%), upper extremity (6, 16%), or pelvis (1, 3%). Thirty patients (81%) developed NP and 26 of them required NP-specific medications (87.7%). The mean [standard deviation (SD)] duration of NP was 6.5 weeks (7.2) (median 4.4, range 0.3–29.9). All 26 patients (27 surgeries) treated with NP medications received gabapentin, either as single therapy (65.4%) (17 patients, 18 surgeries), dual therapy with gabapentin and amitriptyline (five patients), or triple therapy with gabapentin, amitriptyline, and methadone (four patients). The mean starting (maximum) doses of gabapentin, amitriptyline, and methadone (mg/kg/day) were 20.2 (43.8), 0.5 (0.7), and 0.3 (0.3), respectively. The incidence and duration of NP, duration of treatment, and NP-specific dose regimens were similar in the limb sparing and the amputation groups. Conclusions NP after definitive surgery for OS is frequently encountered, can persist for a significant time, and NP outcomes are similar in limb sparing and amputation groups.

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Section: Discussionmentioning

confidence: 99%

Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population

Anghelescu

Steen

et al. 2016

Pediatric Blood & Cancer

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“…alleviated cisplatin-evoked mechanical allodynia and cold allodynia in the hindpaws of rats (Guindon et al, 2013) and mice (Namvaran-Abbas-Abad and Tavakkoli, 2012). Although there have been no trials of opioids in patients with CIPN (Park et al, 2010), the combination of gabapentin with opioids for the management of pain because of CIPN appears promising (Keskinbora et al, 2007;Arai et al, 2010;Patarica-Huber et al, 2011). produced partial pain relief, whereas morphine at 4 mg/kg i.p.…”

Section: Discussionmentioning

confidence: 99%

Optimization and pharmacological characterization of a refined cisplatin-induced rat model of peripheral neuropathic pain

Han

Wyse

Smith

2014

Behavioural Pharmacology

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Chemotherapy-induced peripheral neuropathy (CIPN) is the major dose-limiting side-effect of many front-line anticancer drugs. This study was designed to establish and pharmacologically characterize a refined rat model of cisplatin-induced CIPN. Adult male Sprague-Dawley rats received four (n=18) or five (n=18) single intraperitoneal bolus doses of cisplatin at 3 mg/kg, or saline (control group), once-weekly. Body weight and general health were assessed over a 49-day study period. von Frey filaments and the Hargreaves test were used to define the time course for the development of mechanical allodynia and thermal hypoalgesia in the hindpaws and for efficacy assessment of analgesic/adjuvant agents. The general health of rats administered four cisplatin doses was superior to that of rats administered five doses. Mechanical allodynia was fully developed (paw withdrawal thresholds≤6 g) in the bilateral hindpaws from day 32 to 49 for both cisplatin dosing regimens. They also showed significant thermal hypoalgesia in the bilateral hindpaws. In cisplatin-treated rats with paw withdrawal thresholds of up to 6 g, single bolus doses of gabapentin and morphine produced dose-dependent analgesia, whereas meloxicam and amitriptyline lacked efficacy. We have established and pharmacologically characterized a refined rat model of CIPN that is suitable for efficacy profiling of compounds from analgesic discovery programmes.

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“…183 Similarly, low dose of gabapentin (400 mg) has been characterized as useful adjuvant to opioids for NCP when combined with low dose of imipramine (40 mg), leading to a significant reduction of pain and severe adverse events. 184 In a recent study 818 NCP patients were treated according to the WHO analgesic ladder, having a follow-up of 6 months. 185 The researchers used adjuvant drugs such as amitryptiline (29.9%), gabapentin (29.9%), gabapentin and dexamethasone (19.9%) and dexamethasone (20.2%).…”

Section: 155mentioning

confidence: 99%

Pharmacological Treatment of Neuropathic Cancer Pain: A Comprehensive Review of the Current Literature

et al. 2011

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Neuropathic cancer pain (NCP), commonly encountered in clinical practice, may be cancer-related, namely resulting from nervous system tumor invasion, surgical nerve damage during tumor removal, radiation-induced nerve damage and chemotherapy-related neuropathy, or may be of benign origin, unrelated to cancer. A neuropathic component is evident in about 1/3 of cancer pain cases.Although from a pathophysiological perspective NCP may differ from chronic neuropathic pain (NP), such as noncancer-related pain, clinical practice, and limited publications have shown that these two pain entities may share some treatment modalities. For example, co-analgesics have been well integrated into cancer pain-management strategies and are often used as First-Line options for the treatment of NCP. These drugs, including antidepressants and anticonvulsants, are recommended by evidence-based guidelines, whereas, others such as lidocaine patch 5%, are supported by randomized, controlled, clinical data and are included in guidelines for restricted conditions treatment. The vast majority of these drugs have already been proven useful in the management of benign NP syndromes. Treatment decisions for patients with NP can be difficult. The intrinsic difficulties in performing randomized controlled trials in cancer pain have traditionally justified the acceptance of drugs already known to be effective in benign NP for the management of malignant NP, despite the lack of relevant high quality data. Interest in NCP mechanisms and pharmacotherapy has increased, resulting in significant mechanism-based treatment advances for the future. In this comprehensive review, we present the latest knowledge regarding NCP pharmacological management. n INTRODUCTIONFollowing EFIC's (European Federation of IASP Chapters) declaration in 2001, pain is not a symptom but a disease in its own right, necessitating appropriate treatment. The word pain usually refers to a discrete sensory experience, triggered by an identifiable set of ''painful'' stimuli, acting on a unique or stable ''pain'' pathway and eliciting an invariant sensation. However, pain, and particularly neuropathic pain (NP) can also exist as a diverse group of complex phenomena of unpleasant and distressing nature. NP encloses numerous complicated neurobiologic constituents and reflects potentially dynamic mechanisms, interacting at multiple neuraxial sites. 1Modern neurobiological techniques have led to tremendous progress in the exploration of pain pathogenetic mechanisms. [2][3][4] Research indicates that pain can be produced in multiple ways, at different locations, co-existing between and across various pathological conditions. 5,6 Novel therapeutic targets have been discovered and are used by the pharmaceutical industry for the construction of highly specific molecules, acting as potential innovative analgesics. Recent targets' application, specific to precise NP mechanisms, will very soon enable treatment to be focused at particular mechanisms, introducing a mechanism-based therap...

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Low-dose gabapentin as useful adjuvant to opioids for neuropathic cancer pain when combined with low-dose imipramine

Abstract: Low-dose gabapentin-antidepressant combination with opioids was effective in managing neuropathic cancer pain without severe adverse effects.

Cited by 42 publications

References 19 publications

Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population

Prospective study of neuropathic pain after definitive surgery for extremity osteosarcoma in a pediatric population

Optimization and pharmacological characterization of a refined cisplatin-induced rat model of peripheral neuropathic pain

Pharmacological Treatment of Neuropathic Cancer Pain: A Comprehensive Review of the Current Literature

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