Korean J Pain.  2006 Jun;19(1):33-44. 10.3344/kjp.2006.19.1.33.

Role of Peripheral Glutamate Receptors to Mechanical Hyperalgesia following Nerve Injury or Antidromic Stimulation of L5 Spinal Nerve in Rats with the Previous L5 Dorsal Rhizotomy

• Jang JH
• Nam TS
• Yoon DM
• Leem JW
• Paik GS

• KMID: 2278013
• DOI: http://doi.org/10.3344/kjp.2006.19.1.33

Abstract

BACKGROUND: Peripheral nerve injury leads to neuropathic pain, including mechanical hyperalgesia (MH). Nerve discharges produced by an injury to the primary afferents cause the release of glutamate from both central and peripheral terminals. While the role of centrally released glutamate in MH has been well studied, relatively little is known about its peripheral role. This study was carried out to determine if the peripherally conducting nerve impulses and peripheral glutamate receptors contribute to the generation of neuropathic pain.
METHODS
Rats that had previously received a left L5 dorsal rhizotomy were subjected to a spinal nerve lesion (SNL) or brief electrical stimulation (ES, 4 Hz pulses for 5 min) of the left L5 spinal nerve. The paw withdrawal threshold (PWT) to von Frey filaments was measured. The effects of an intraplantar (i.pl.) injection of a glutamate receptor (GluR) antagonist or agonist on the changes in the SNL- or ES-produced PWT was investigated.
RESULTS
SNL produced MH, as evidenced by decrease in the PWT, which lasted for more than 42 days. ES also produced MH lasting for 7 days. MK-801 (NMDAR antagonist), DL-AP3 (group-I mGluR antagonist), and APDC (group-II mGluR agonist) delayed the onset of MH when an i.pl. injection was given before SNL. The same application blocked the onset of ES-induced MH. NBQX (AMPA receptor antagonist) had no effect on either the SNL- or ES-induced onset of MH. When drugs were given after SNL or ES, MK-801 reversed the MH, whereas NBQX, DL-AP3, and APDC had no effect.
CONCLUSIONS
Peripherally conducting impulses play an important role in the generation of neuropathic pain, which is mediated by the peripheral glutamate receptors.

Keyword

electrical stimulation; glutamate; injury discharge; nerve injury; neuropathic pain

MeSH Terms

Action Potentials
Animals
Dizocilpine Maleate
Electric Stimulation
Glutamic Acid*
Hyperalgesia*
Neuralgia
Peripheral Nerve Injuries
Rats*
Receptors, Glutamate*
Rhizotomy*
Spinal Nerves*
Dizocilpine Maleate
Glutamic Acid
Receptors, Glutamate