Paroxetine ameliorates whole-body allodynia

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]. Among the neuropathic pain subtypes in diabetes neuropathy, allodynia is refractory to duloxetine and the clinical therapeutic strategy for allodynia still remains controversial [5]. We present two cases of whole-body allodynia that drastically recovered using paroxetine. This is the first report to feature the notable effect of paroxetine on allodynia in humans. …