Attenuation of pain behaviour by local administration of alpha-2 adrenoceptor antagonists to dorsal root ganglia in a rat radiculopathy model.
BACKGROUND
There were several reports suggesting α-adrenoceptor antagonists are effective to treat neuropathic pain. The aims of this study were as follows: (1) to introduce drug delivery system for dorsal root ganglion (DRG) neurons; (2) to elucidate the effects of α-adrenoceptor antagonists in acute, subacute or chronic phase and (3) to determine which subtype of adrenoceptor was mainly involved.


METHODS
We used 130 male Sprague-Dawley rats. After root constriction, rats received three local injections of α-adrenoceptor antagonists around DRG. We administered the non-selective α-adrenoceptor antagonist phentolamine for 3 consecutive days from day 0, 4 or 11 after the surgery, and the α1-adrenoceptor antagonist prazosin, the α1-adrenoceptor antagonist silodosin, the more preferred α1-adrenoceptor than prazosin and the α2-adrenoceptor antagonist yohimbine for 3 consecutive days from day 0 after the surgery.


RESULTS
Phentolamine and yohimbine continually attenuated pain behaviour. Prazosin at high dose attenuated pain behaviour, however, prazosin at low dose did not attenuate pain behaviour every experimental day. Silodosin had no analgesic effect. Phentolamine injections from day 4 after surgery attenuated pain behaviour that had been established on the 3rd experimental day until the 28th post-operative day, although effect of phentolamine wore off. Phentolamine injections from day 11 after surgery temporarily attenuated pain behaviour that had been established on the 3rd, 7th and 10th experimental days.


CONCLUSIONS
This study showed α-adrenoceptor antagonists could suppress pain behaviour via α2-adrenoceptor in acute phase and temporary attenuate pain behaviour in chronic phase. These findings presented potentials sympathetic nerve blockade contributed to treat neuropathic pain.
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
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I
Ogon
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
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T
Takebayashi
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
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T
Miyakawa
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
T
T
Iwase
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
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Tanimoto
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
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Y
Terashima
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
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S
Jimbo
Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Japan.
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T
Kobayashi
Department of Cellular Physiology and Signal Transduction, Sapporo Medical University School of Medicine, Japan.
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N
Tohse
Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, Japan.
T
T
Yamashita
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D005727:Ganglia, Spinal / Q000293:injuries*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009437:Neuralgia; D010147:Pain Measurement; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011843:Radiculopathy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015016:Yohimbine / Q000494:pharmacology
D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D015016:Yohimbine; C095285:silodosin; D011224:Prazosin; D010646:Phentolamine