1.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.
Jun Ho JANG ; Taick Sang NAM ; Duck Mi YOON ; Joong Woo LEEM ; Gwang Se PAIK
The Korean Journal of Pain 2006;19(1):33-44
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.
Action Potentials
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Animals
;
Dizocilpine Maleate
;
Electric Stimulation
;
Glutamic Acid*
;
Hyperalgesia*
;
Neuralgia
;
Peripheral Nerve Injuries
;
Rats*
;
Receptors, Glutamate*
;
Rhizotomy*
;
Spinal Nerves*
2.Spinal and Peripheral GABA-A and B Receptor Agonists for the Alleviation of Mechanical Hypersensitivity following Compressive Nerve Injury in the Rat.
Young Hoon JEON ; Duck Mi YOON ; Taick Sang NAM ; Joong Woo LEEM ; Gwang Se PAIK
The Korean Journal of Pain 2006;19(1):22-32
BACKGROUND: This study was conducted to investigate the roles of the spinal and peripheral gamma-aminobutyric acid (GABA)-ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). METHODS: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. RESULTS: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. CONCLUSIONS: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.
Animals
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Back Pain
;
Baclofen
;
Bicuculline
;
GABA-A Receptor Agonists
;
GABA-A Receptor Antagonists
;
GABA-B Receptor Agonists
;
gamma-Aminobutyric Acid
;
Ganglia, Spinal
;
Hyperalgesia
;
Hypersensitivity*
;
Muscimol
;
Neuralgia
;
Posterior Horn Cells
;
Rats*
;
Receptors, GABA
;
Spinal Cord