title: P2X3 receptor mediates heat hyperalgesia in a rat model of trigeminal neuropathic pain.
abstract: The present study was undertaken to determine the role of P2X3 receptor (P2X3R) on heat hyperalgesia in a newly developed rat model of trigeminal neuropathic pain. The unilateral infraorbital nerve (IoN) was partially ligated by 6-0 silk. To assess heat sensitivity, a vibrissal pad (VP) was placed on a hot plate and the latency until the rats withdrew their head was measured. Mechanical sensitivity of VP was also assessed by the use of von Frey filament. Both heat and mechanical hyperalgesia were observed at the VP ipsilateral to the IoN ligation. The latency to heat stimuli was prolonged after subcutaneous administration of pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, P2X1,2,3,5,7,1/5,2/3R antagonist) and 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP, P2X1,3,2/3,1/5R antagonist). The latency was shortened after administration of alpha,beta-methylene ATP (alpha,beta-meATP, P2X1,3,2/3R agonist), although no changes appeared after administration of beta,gamma-methylene-L-ATP (beta,gamma-me-L-ATP, P2X1R agonist). The protein gene product-9.5 and calcitonin gene-related peptide immunoreactive nerve fibers significantly decreased in the VP skin of ipsilateral to the IoN ligation. In the ipsilateral trigeminal ganglion, the number of P2X3-immunoreactive neurons significantly increased in the small cell group. In this study, we developed an experimental model of trigeminal neuropathic pain by partial ligation of IoN, which produced heat and mechanical hyperalgesia in the VP. Pharmacological and immunohistochemical studies revealed that the P2X3R plays an important role in the heat hyperalgesia observed in this model.
  
  
  CONCLUSIONS
  The study describes the development of a novel model of trigeminal neuropathic pain. Heat hyperalgesia in this model was inhibited by peripheral injection of P2XR antagonists. The results suggest that P2X3R is a potential target for development of a novel therapy for trigeminal neuropathic pain.
authors.affiliation: Department of Functional Anatomy and Neuroscience, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Shinoda
authors.forename: Kiyohito
authors.initials: K
authors.lastname: Kawashima
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ozaki
authors.forename: Hideaki
authors.initials: H
authors.lastname: Asai
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Nagamine
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Sugiura
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004195:Disease Models, Animal; D006930:Hyperalgesia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008026:Ligation; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000378:metabolism; D014276:Trigeminal Nerve / Q000378:metabolism* / Q000503:physiopathology; D014277:Trigeminal Neuralgia / Q000378:metabolism* / Q000503:physiopathology; D043222:Ubiquitin Thiolesterase / Q000378:metabolism
chemical_list: C546410:P2rx3 protein, rat; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D000255:Adenosine Triphosphate; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase; D015740:Calcitonin Gene-Related Peptide