Article

Therapy of chemotherapy-induced peripheral neuropathy

Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
British Journal of Haematology (Impact Factor: 4.96). 02/2009; 145(1):3-14. DOI: 10.1111/j.1365-2141.2008.07558.x
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ABSTRACT Chemotherapy-induced peripheral neuropathy (CIPN) is still a common and disabling side effect of many chemotherapy agents in use today. Unfortunately, neither prophylactic strategies nor symptomatic treatments have proven useful yet. This review will discuss the diagnosis and evaluation of neuropathy in cancer patients, as well as reviewing the various prophylactic and symptomatic treatments that have been proposed or tried. However, sufficient evidence is lacking to recommend any of these treatments to patients suffering with CIPN. Therefore, the best approach is to treat symptomatically, and to start with broad-spectrum analgesic medications such as non-steroidal anti-inflammatory drugs (NSAIDs). If NSAIDs fail, a reasonable second-line agent in properly selected patients may be an opioid. Unfortunately, even when effective in other types of neuropathic pain, anti-depressants and anticonvulsants have not yet proven effective for treating the symptoms of CIPN.

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    • "As there is no specific, reliable diagnostic test of CIPN, the diagnosis is currently based on clinical criteria: a combination of clinical symptoms and signs, electrophysiological measurements (EPM) and quantitative sensory tests (QST). However, conventional EPM's such as nerve conduction velocity (NCV) and electromyography (EMG) may be normal in the presence of small nerve fibre damage (Sissung et al. 2008) and are therefore considered complimentary rather than diagnostic (Kaley and Deangelis 2009). Moreover, they show poor correlation with severity of clinical symptoms (Berger et al. 1997) and have failed to demonstrate any clear benefit over simple clinical symptom-scoring systems for monitoring the condition (du Bois et al. 1999; Mileshkin et al. 2006). "
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    ABSTRACT: IntroductionThe diagnosis and quantification of chemotherapy-induced peripheral neuropathy (CIPN) remains a challenge. Conventional methods including quantitative sensory testing (QST), nerve conduction tests, and biopsy are unable to detect subclinical changes, and do not consistently correlate with severity of patients' symptoms and functional impairment. This study aims to determine the utility of the LDI (laser Doppler imager) FLARE technique in the diagnosis of CIPN and whether it correlates with symptom severity.Materials and Methods We assessed 24 patients with established CIPN [12 due to platinum analogs (PA) and 12 to Taxanes (TX)] and 24 matched healthy controls (HC). All underwent neurophysiological examination including vibration perception threshold (VPT), sural nerve amplitude (SNAP) and conduction velocity (SNCV), LDIFLARE, and fasting biochemistry. The QLQ-CIPN20 questionnaire was used to assess symptom severity.ResultsHC, combined chemotherapy (CG), PA, and TX groups were matched for age, sex, BMI, and blood pressure. The LDIFLARE was significantly reduced in CG compared to HC (P =< 0.0001), whereas SNAP (P = 0.058) and SNCV (P = 0.054) were not. The LDIFLARE correlated with the QLQ-CIPN20 symptom scores in all three categories namely, CG (P =< 0.0001), PA (P = 0.001) and TX (P = 0.027) whilst, VPT, SNAP, and SNCV did not.Conclusion Our findings suggest that the LDIFLARE technique is more helpful in confirming the diagnosis of CIPN in patients with distal sensory symptoms than current commonly used methods. Moreover, this novel test fulfils the unmet need for a diagnostic test that relates to the severity of symptoms. This may be useful in quantifying early changes in small fibre function indicating early CIPN.
    Brain and Behavior 05/2015; 5(7). DOI:10.1002/brb3.354
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    • "Cold hypersensitivity and hyperalgesia are often symptoms of several neuropathic conditions, including complex regional pain syndrome and trigeminal neuralgia, peripheral nerve injury (Maier et al., 2010), and also chemotherapy-induced neuropathy where cancer treatment is often limited because of adverse effects and the resulting neuropathy is largely undertreated by currently available drugs (Kaley and DeAngelis, 2009). Cold hypoaesthesia can exist alongside cold hyperalgesia; patients often describe pain elicited by low temperatures as having a burning quality (Ochoa and Yarnitsky, 1994). "
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    ABSTRACT: Abnormal cold sensitivity is a common feature of a range of neuropathies. In the murine somatosensory system, multiple aspects of cold sensitivity are dependent on TRPM8, both acutely and in response to peripheral nerve injury. The specialised nature of cold sensitive afferents and the restricted expression of TRPM8 render it an attractive target for the treatment of cold hypersensitivity. This current study examines the effect of a novel TRPM8 antagonist (M8-An) in naïve and spinal nerve ligated rats through behavioural and in vivo electrophysiological approaches. In vitro, M8-An inhibited icilin evoked Ca(2+) currents in HEK293 cells stably expressing human TRPM8 with an IC50 of 10.9 nM. In vivo, systemic M8-An transiently decreased core body temperature. Deep dorsal horn recordings were made in vivo from neurones innervating the hind paw. M8-An inhibited neuronal responses to innocuous and noxious cooling of the receptive field in spinal nerve ligated rats, but not in naive rats. No effect on neuronal responses to mechanical and heat stimulation was observed. In addition, M8-An also attenuated behavioural responses to cold but not mechanical stimulation after nerve ligation without affecting the uninjured contralateral response. The data presented here supports a contribution of TRPM8 to the pathophysiology of cold hypersensitivity in this model and highlights the potential of the pharmacological block of TRPM8 in alleviating the associated symptoms.
    Journal of Pharmacology and Experimental Therapeutics 01/2014; 349(1). DOI:10.1124/jpet.113.211243 · 3.86 Impact Factor
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    • "Treatment with many cancer chemotherapies is limited by their dose-related peripheral nervous system toxicity, a small-fiber painful peripheral neuropathy. The most frequently reported agents include many older commonly used chemotherapeutic agents, such as platinum drugs, taxanes, epothilones and vinca alkaloids, but also newer agents, such as bortezomib and lenolidamide (Abrey and Correa, 2005; Kaley and Deangelis, 2009; Stillman and Cata, 2006; Sul and Deangelis, 2006; Wolf et al., 2008). "
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    ABSTRACT: Vincristine-induced peripheral neuropathy is a major dose limiting side effect and thus, effective therapeutic strategy is required. In this study, the antinociceptive effect of Matricaria chamomilla (MC) hydroalcoholic extract and morphine on vincristine-induced peripheral neuropathy model in mice has been investigated. Experiments were performed on 60 Naval Medical Research Institute (NMRI) male mice. Mouse subsequently received daily intraperitoneal and intravenal injections of vincristine sulfate, saline and MC hydroalcoholic extract over 12 days, immediately following behavioral testing. For assessment of pain, formalin test was preformed. The effects of MC, morphine and vehicle (saline) 30 min before formalin test on vincristine-induced neuropathy were evaluated. Administration of MC before formalin injection showed significant (P < 0.05) decrease of pain responses in both phases. Administration of vincristine produced significant (Pm < 0.05) increase in pain response in second phase of formalin test. Injection of MC and vincristine together has shown that MC is able to decrease the vincristine induced pain significantly (P < 0.05). Morphine decreased vincristine induced pain test significantly (P < 0.05). In comparison, morphine has analgesic effects in the first phase and MC has anti-inflammatory effects in the second phase of formalin test significantly (P < 0.05). These results suggest that MC may be an alternative approach for the treatment of vincristine-induced peripheral neuropathic pain.
    African journal of pharmacy and pharmacology 01/2012; 6(1):24-29. · 0.84 Impact Factor
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