Immunocytochemical localization of P2X3 purinoceptors in sensory neurons in naive rats and following neuropathic injury

Abstract

P2X3 purinoceptor cellular distribution was studied in rat sensory neurons in naive animals and following peripheral nerve injury using immunohistochemical methods. Specific antiserum was raised in rabbits and characterized by Western blot, absorption assays and labeling of recombinant receptors. In naive animals, P2X3 immunoreactivity was present predominantly in a subpopulation of small-diameter sensory neurons in dorsal root ganglia. In the spinal cord, immunoreactivity was observed in the superficial laminae of the dorsal horn. Following a chronic constriction injury to the sciatic nerve, the number of P2X3 positive small and medium diameter neurons increased in dorsal root ganglia when compared with sham-operated animals. In addition, the spinal cord immunoreactivity increased in magnitude on the side ipsilateral to the ligated nerve, consistent with up-regulation of receptors in presynaptic terminals of the primary sensory neurons.

Nanoparticle-encapsulated emodin decreases diabetic neuropathic pain probably via a mechanism involving P2X3 receptor in the dorsal root ganglia

“…The P2X3 receptor is expressed in small diameter neurons of the DRG [11, 14-17, 19, 34]. Damage to peripheral nerves in neuropathic pain state can enhance expression levels of the P2X3 receptor [11,[14][15][16]34]. The present study demonstrated that the expression of P2X3 protein and mRNA in the T2DM DRG is upregulated compared to controls.…”

“…The P2X3 receptor is most highly expressed in a subpopulation of small diameter primary afferent neurons. The expression of P2X3 protein and messenger RNA (mRNA) is increased following chronic constriction injury (CCI) of the sciatic nerve [11][12][13][14][15][16][17][18]. The P2X3 receptor plays a crucial role in chronic neuropathic pain [11][12][13][15][16][17][18][19], and this receptor has been shown to mediate mechanical allodynia in diabetic neuropathic rats [20].…”

Effects of A‐317491, a novel and selective P2X3/P2X2/3 receptor antagonist, on neuropathic, inflammatory and chemogenic nociception following intrathecal and intraplantar administration

“…The site of this action is likely on the primary afferent terminals located in the superficial laminae of the dorsal horn (Cook et al, 1997;Vulchanova et al, 1997). Immunolabeling of the P2X 3 receptor has been observed in the upper laminae of naı¨ve animals, and is increased following CCI procedures (Novakovic et al, 1999). Despite a decrease in P2X 3 immunoreactivity in the dorsal root ganglion of animals with L5 -L6 ligations , the spinal effects of A-317491 in this model may be mediated via the spared dorsal horn terminals of L4 afferents, and/or by the terminals of IB4 negative large-diameter L5 -L6 neurons .…”

“…These receptors are highly expressed in dorsal root ganglion neurons, particularly in small-diameter sensory neurons (Chen et al, 1995). Neuronal expression of the P2X 3 receptor is elevated in both the dorsal root ganglion and the ipsilateral spinal cord following chronic constriction injury (CCI) of the sciatic nerve (Novakovic et al, 1999). Furthermore, P2X 3 (À/À) gene-ablated mice show a significant attenuation in spontaneous pain behaviors following administration of ATP or formalin (Cockayne et al, 2000;Souslova et al, 2000), and animals treated with P2X 3 antisense oligonucleotides exhibit reduced thermal hyperalgesia and mechanical allodynia (Barclay et al, 2002;Honore et al, 2002).…”

Inhibitory effect of estrogen receptor beta on P2X3 receptors during inflammation in rats

“…It is well accepted that up-regulated expression and enhanced activity of P2X3R in DRG neurons is closely associated with the development and maintenance of acute and chronic pain [42,43]. Activation of P2X3R stimulates different cells, such as neurons or immunocytes, to cause abnormal excitability [23,25] or release inflammatory mediators, including TNFα, to induce inflammation [26].…”