European Journal of Clinical Pharmacology

, Volume 74, Issue 7, pp 979–980 | Cite as

Paroxetine ameliorates whole-body allodynia

  • Hiroki Shiwaku
  • Toru Nishikawa
Letter to the Editor

Allodynia is one of the features of neuropathic pain, but its therapy is still insufficient [1]. Among the pathological mechanisms of neuropathic pain, the involvement of microglia has been well investigated. Especially, the upregulation of the P2X4 receptor, an ionotropic ATP receptor, in the microglia is a key molecular mechanism [2]. Paroxetine has a remarkable antagonistic potential for the P2X4 receptor [3]. Although the reported IC50 values for inhibition of the receptor function are similar between paroxetine (1.87 μM) [3] and duloxetine (1.59 μM) [4], paroxetine causes a slightly more complete attenuation of the P2X4 receptor function (to approximately 4% of control response of the receptor) than duloxetine (to about 9%) [4] that is one of the recommended drugs for the treatment of neuropathic pain. Indeed, paroxetine relieves allodynia in rodent models [3]. However, a recent therapeutic strategy for neuropathic pain does not mention such an analgesic effect of paroxetine [1]....


  1. 1.
    Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M (2015) Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol 14(2):162–173CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Beggs S, Trang T, Salter MW (2012) P2X4R+ microglia drive neuropathic pain. Nat Neurosci 15(8):1068–1073CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Nagata K, Imai T, Yamashita T, Tsuda M, Tozaki-Saitoh H, Inoue K (2009) Antidepressants inhibit P2X4 receptor function: a possible involvement in neuropathic pain relief. Mol Pain 5:20CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Yamashita T, Yamamoto S, Zhang J, Kometani M, Tomiyama D, Kohno K, Tozaki-Saitoh H, Inoue K, Tsuda M (2016) Duloxetine inhibits microglial P2X4 receptor function and alleviates neuropathic pain after peripheral nerve injury. PLoS One 11(10):e0165189CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Wernicke JF, Pritchett YL, D'Souza DN, Waninger A, Tran P, Iyengar S, Raskin J (2006) A randomized controlled trial of duloxetine in diabetic peripheral neuropathic pain. Neurology 67(8):1411–1420CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Psychiatry and Behavioral SciencesTokyo Medical and Dental University Graduate SchoolTokyoJapan

Personalised recommendations