[Painful hyperexcitability syndrome with oxaliplatin containing chemotherapy. Clinical features, pathophysiology and therapeutic options].

Neurologische Klinik, Knappschaftskrankenhaus Bochum-Langendreer, Ruhr-Universität Bochum, In der Schornau 23-25, 44892, Bochum, Deutschland.
Der Schmerz (Impact Factor: 1.02). 03/2008; 22(1):16-23.
Source: PubMed


The platinum derivative oxaliplatin is widely used in colorectal cancer. Its side effects differ from those of the other platinum compounds cisplatin and carboplatin. An acute, painful hyperexcitability syndrome (HES) accompanied by cold induced paresthesia, dysesthesia and myotonia is unique to oxaliplatin, whereas a chronic, peripheral sensory neuropathy (PSN) can be caused by all platinum compounds. It is believed that HES is the result of peripheral nerve hyperexcitability as a consequence of voltage-gated sodium channel dysfunction, which may be caused by calcium level imbalance. Therapeutic options for HES are the administration of calcium and magnesium, the serotonin and noradrenaline reuptake inhibitor (SNRI) venlafaxine and the thiophosphate amifostine.

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    • "Inflammatory pain was produced by focal intradermal injection of carrageenan on the dorsum of the hind paw (Guilbaud et al., 1989a; Guilbaud et al., 1989b; Dawson et al., 1991; Aley et al., 2000; Khasar et al., 2008). Three neuropathic pain models were tested; one of these was a model of alcoholic painful peripheral neuropathy (Diamond and Messing, 1994; Monforte et al., 1995; Kielhorn, 1996; Ortiz-Plata et al., 1998; Dina et al., 2000); and two models (early and late phase neuropathy) were induced by intravenous injection of the chemotherapeutic agent oxaliplatin (Joseph et al., 2008; Kowalski et al., 2008). Enhanced cytokine hyperalgesia, a model of chronic widespread pain syndromes such as fibromyalgia (Khasar et al., 2005) was induced by cytokine administration after chronic unpredictable stress. "
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    ABSTRACT: Analgesic efficacy varies depending on the pain syndrome being treated. One reason for this may be a differential effect of individual pain syndromes on the function of the endogenous pain control circuits at which these drugs act to produce analgesia. To test this hypothesis, we examined the effects of diverse (i.e., ongoing inflammatory, neuropathic, or chronic widespread) pain syndromes on analgesia induced by activation of an opioid-mediated, noxious stimulus-induced endogenous pain control circuit. This circuit was activated by subdermal capsaicin injection at a site remote from the site of nociceptive testing. Analgesia was not affected by carrageenan-induced inflammatory pain or the early phase of oxaliplatin neuropathy (a complication of cancer chemotherapy). However, the duration of analgesia was markedly shorter in the late phase of oxaliplatin neuropathy and in alcoholic neuropathy. A model of fibromyalgia syndrome produced by chronic unpredictable stress and proinflammatory cytokines also shortened analgesia duration, but so did the same stress alone. Therefore, since chronic pain can activate neuroendocrine stress axes, we tested whether they are involved in the attenuation of analgesic duration induced by these pain syndromes. Rats in which the sympathoadrenal axis was ablated by adrenal medullectomy showed normal duration pain-induced analgesia in groups with either late-phase oxaliplatin neuropathy, alcoholic neuropathy, or exposure to sound stress. These results support the suggestion that pain syndromes can modulate activity in endogenous pain control circuits and that this effect is sympathoadrenal dependent.
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