Etanercept reduced hyperalgesia in experimental painful neuropathy. J Peripher Nerv Syst 6:67-72

Department of Neurology, University of Würzburg, Germany.
Journal of the Peripheral Nervous System (Impact Factor: 2.5). 07/2001; 6(2):67-72. DOI: 10.1046/j.1529-8027.2001.01010.x
Source: PubMed

ABSTRACT Etanercept, a recombinant tumor necrosis factor receptor (p75)-Fc fusion protein competitively inhibits tumor necrosis factor-alpha (TNF). Etanercept has been successfully used in patients with rheumatoid arthritis, where it reduces pain and inflammation. Because locally produced proinflammatory cytokines play a role in pain after nerve injury, we investigated whether etanercept can reduce pain and hyperalgesia in an animal model of painful neuropathy, the chronic constriction injury of the sciatic nerve. C57BL/6 mice received etanercept or sham treatment by local near-nerve injection to the injured nerve or by systemic application. Treatment with etanercept reduced thermal hyperalgesia and mechanical allodynia significantly in both modes of application. The effect of etanercept was present in animals that were treated from the time of surgery and in those that were treated from day 6, when hyperalgesia was already present. These results suggest the potential of etanercept as a treatment option for patients with neuropathic pain.

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    • "On the other hand, Schäfers and co-workers showed that the treatment with Eta starting on day 1 or 7 after the spinal nerve ligation was ineffective in attenuating the paw mechanical hyperalgesia (Schafers et al., 2003). However, the same group observed in a previous study that Eta reduced the hyperalgesia 6 days after the sciatic constriction injury in the mouse (Sommer et al., 2001). The effect of Eta in orofacial mechanical hyperalgesia in our study was particularly interesting. "
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    ABSTRACT: This study evaluated the involvement of tumour necrosis factor α (TNF-α) in orofacial thermal and mechanical hyperalgesia induced by an inflammatory stimulus or by chronic constriction of the infraorbital nerve (CION) using etanercept (Eta), a TNF-receptor fusion protein that inhibits TNF-α action. Animals were treated with Eta (0.5 and 5.0 mg/kg, s.c.) or dexamethasone (Dex, 0.5, 1.0 and 2.0 mg/kg, s.c.) and orofacial thermal (cold and heat) and mechanical hyperalgesia induced by an inflammatory stimulus (carrageenan, Cg 50 and 100 μg/lip) or by chronic CION, a model of neuropathic pain in the orofacial region was evaluated. Treatments with Dex or Eta were carried out before Cg or before or after CION. Eta or Dex abolished inflammatory thermal and mechanical hyperalgesia. Also, each drug, when given at the day of the surgery and the subsequent day, was effective to abolish thermal and mechanical hyperalgesia induced by CION, assessed on day 4 and on day 13 after the surgery, respectively. However, Eta, but not Dex, given after the CION, abolished thermal and mechanical hyperalgesia and reduced TNF-α level in the trigeminal ganglion. These results suggest that TNF-α has an important role in cold, heat and mechanical hyperalgesia induced by inflammation or neuropathy in the orofacial region and this may contribute for the establishment of new therapeutic strategies to treat orofacial pain.
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    • "In animal models, the administration of the proinflammatory cytokines TNF-α and IL-1β induces pain behavior (31), and treatment with anti-inflammatory cytokines or proinflammatory cytokine inhibitors has been shown to reduce pain (32,33). Human studies show a possible pathogenic role of cytokines in pain. "
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    Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica ... [et al.] 07/2014; 47(7):600-604. DOI:10.1590/1414-431X20143599 · 1.08 Impact Factor
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    • "Subsequent studies provided further supportive evidence [159–165]. In 2001, etanercept was shown to reduce hyperalgesia in experimental painful neuropathy [166]. In 2003 and 2004, the first human evidence of the effectiveness of etanercept for treating neurological spinal pain was published [167–170]. "
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