Korean J Physiol Pharmacol.  2010 Dec;14(6):359-364. 10.4196/kjpp.2010.14.6.359.

Sigma-1 Receptor Antagonist BD1047 Reduces Allodynia and Spinal ERK Phosphorylation Following Chronic Compression of Dorsal Root Ganglion in Rats

• Son JS
• Kwon YB

• KMID: 2071706
• DOI: http://doi.org/10.4196/kjpp.2010.14.6.359

Abstract

Many therapeutic roles have been proposed for sigma-1 receptor (Sig-1R), but the involvement of Sig-1R in neuropathic pain has currently not been well explored. The present study aimed to evaluate the anti-nociceptive effect of Sig-1R antagonist (BD1047) in a rat model of chronic compression of the dorsal root ganglion (CCD), which is a model of human foraminal stenosis and radicular pain. When stainless steel rods were inserted into the intervertebral foramen of lumbar vertebrae 4 and 5, the CCD developed reliable mechanical (from 3 day) and cold allodynia (from 1 day) as compared with the sham operation group. The spinal expressions of Sig-1R and phosphorylation of extracellular signal-regulated kinase (pERK) were significantly increased from day 3 to day 14 after CCD surgery, as is consistent with the manifestation of allodynia. The BD 1047 (10, 30, 100 mg/kg) administered on postoperative days 0~5 dose-dependently suppressed both the induction of allodynia and the elevation of the spinal pERK expression in a manner comparable with that of gabapentin (100 mg/kg). At 7 days post-CCD surgery, BD1047 (10, 30, 100 mg/kg) administration also produced anti-nociceptive effects on the mechanical and cold allodynia similar with those of gabapentin (100 mg/kg). Therefore, this data suggested that Sig-1R may play an important role in both the development and maintenance of CCD-induced neuropathy.

Keyword

Allodynia; Dorsal root ganglion; Extracellular signal-regulated kinase; Neuropathic pain; Sigma-1 receptor

MeSH Terms

Amines
Animals
Cold Temperature
Constriction, Pathologic
Cyclohexanecarboxylic Acids
Ethylenediamines
gamma-Aminobutyric Acid
Ganglia, Spinal
Humans
Hyperalgesia
Lumbar Vertebrae
Neuralgia
Phosphorylation
Phosphotransferases
Rats
Receptors, sigma
Salicylamides
Spinal Nerve Roots
Stainless Steel
Amines
Cyclohexanecarboxylic Acids
Ethylenediamines
Phosphotransferases
Receptors, sigma
Salicylamides
Stainless Steel
gamma-Aminobutyric Acid

Figure

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  Fig. 1. Repeated daily (from days 0 to 5) oral administration of BD1047 (10, 30, 100 mg/kg) or gabapentin (100 mg/kg) prevented mechanical allodynia (A) and cold allodynia (B) following chronic compression of dorsal root ganglion (CCD). ∗p <0.05, ∗∗p<0.01 compared to CCD-Vehicle group. Each group contains 7 animals.

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  Fig. 2. Western blotting analysis illustrating the change of sigma-1 receptor (Sig-1R) expression in the ipsilateral dorsal quadrant of L4-L6 spinal cords after following chronic compression of dorsal root ganglion (n=5 at each time point). ∗∗p<0.01 compared to control group (0 day).

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  Fig. 3. Western blotting analysis of the effect of daily BD1047 treatment (100 mg/kg, 0∼5 day) on chronic compression of dorsal root ganglion (CCD) induced ERK1/2 expression and phosphorylated ERK1/2 (pERK) in the ipsilateral dorsal quadrant of L4-L6 spinal cords (n=5 at each time point in each group). ∗∗p<0.01 compared to control group (0 day).

• 

  Fig. 4. Oral administration of BD1047 (10, 30, 100 mg/kg) or gabapentin (100 mg/kg) suppressed mechanical allodynia (A) and cold allodynia (B) at 7 day after chronic compression of dorsal root ganglion (CCD). ∗p<0.05, ∗∗p<0.01 compared to Vehicle group. Each group contains 7 animals.

Reference

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