Int J Oral Biol.  2017 Sep;42(3):129-135. 10.11620/IJOB.2017.42.3.129.

Blockade of Trigeminal Glutamate Recycling Produces Anti-allodynic Effects in Rats with Inflammatory and Neuropathic Pain

Affiliations
  • 1Department of Oral Physiology, School of Dentistry, Kyungpook National University, Daegu, Korea. dkahn@knu.ac.kr
  • 2Department of Dental Hygiene, Dong-Eui University, Busan, Korea.
  • 3Department of Dental Hygiene, Kyung-Woon University, Gumi, Korea.

Abstract

The present study investigated the role of spinal glutamate recycling in the development of orofacial inflammatory pain or trigeminal neuropathic pain. Experiments were carried out on male Sprague-Dawley rats weighing between 230 and 280 g. Under anesthesia, a polyethylene tube was implanted in the atlanto-occipital membrane for intracisternal administration. IL-1β-induced inflammation was employed as an orofacial acute inflammatory pain model. IL-1β (10 ng) was injected subcutaneously into one vibrissal pad. We used the trigeminal neuropathic pain animal model produced by chronic constriction injury of the infraorbital nerve. DL-threo-β -benzyloxyaspartate (TBOA) or methionine sulfoximine (MSO) was administered intracisternally to block the spinal glutamate transporter and the glutamine synthetase activity in astroglia. Intracisternal administration of TBOA produced mechanical allodynia in naïve rats, but it significantly attenuated mechanical allodynia in rats with interleukin (IL)-1 β-induced inflammatory pain or trigeminal neuropathic pain. In contrast, intracisternal injection of MSO produced anti-allodynic effects in rats treated with IL-1β or with infraorbital nerve injury. Intracisternal administration of MSO did not produce mechanical allodynia in naive rats. These results suggest that blockade of glutamate recycling induced pro-nociception in naïve rats, but it paradoxically resulted in anti-nociception in rats experiencing inflammatory or neuropathic pain. Moreover, blockade of glutamate reuptake could represent a new therapeutic target for the treatment of chronic pain conditions.

Keyword

glutamate recycling; transporter; MSO; TBOA; trigeminal pain

MeSH Terms

Amino Acid Transport System X-AG
Anesthesia
Animals
Astrocytes
Chronic Pain
Constriction
Glutamate-Ammonia Ligase
Glutamic Acid*
Humans
Hyperalgesia
Inflammation
Interleukins
Male
Membranes
Methionine Sulfoximine
Models, Animal
Neuralgia*
Polyethylene
Rats*
Rats, Sprague-Dawley
Recycling*
Amino Acid Transport System X-AG
Glutamate-Ammonia Ligase
Glutamic Acid
Interleukins
Methionine Sulfoximine
Polyethylene
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