Abstract | BACKGROUND: Noxious stimulus-induced analgesia (NSIA) is a type of conditioned pain modulation in rats that has been used to assess endogenous pain control systems. The descending noradrenergic system is involved in NSIA, and nerve injury induces plastic changes of descending noradrenergic neurons. Thus, we hypothesized that nerve injury would affect NSIA strength and that amitriptyline and pregabalin, which often are used for treating neuropathic pain, might further modulate NSIA through effects on the descending noradrenergic system. METHODS: RESULTS: NSIA was dramatically attenuated 5 and 6 weeks after SNL (P < 0.001). The noradrenaline level in the lumbar spinal cord was significantly increased in noninjured rats receiving forepaw injection of capsaicin compared with vehicle injection (P < 0.001), but not in rats 6 weeks after SNL surgery. Five daily intraperitoneal injections of amitriptyline (10 mg/kg/d) or pregabalin (10 mg/kg/ d) at 5 weeks after SNL gradually increased the ipsilateral hindpaw withdrawal threshold (P < 0.001). At 6 weeks after SNL, amitriptyline, but not pregabalin, reversed the attenuation of NSIA by SNL (P < 0.001) and increased the spinal noradrenaline level after forepaw injection of capsaicin (P = 0.005). CONCLUSIONS: These data suggest that endogenous analgesia in neuropathic pain states is strongly decreased from a certain time after nerve injury and that amitriptyline reverses the attenuation of endogenous analgesia through effects on the descending noradrenergic system.
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Authors | Hiroaki Matsuoka, Takashi Suto, Shigeru Saito, Hideaki Obata |
Journal | Anesthesia and analgesia
(Anesth Analg)
Vol. 123
Issue 2
Pg. 504-10
(08 2016)
ISSN: 1526-7598 [Electronic] United States |
PMID | 27088996
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Analgesics
- Sensory System Agents
- Amitriptyline
- Pregabalin
- Capsaicin
- Norepinephrine
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Topics |
- Adrenergic Neurons
(drug effects, metabolism)
- Amitriptyline
(pharmacology)
- Analgesics
(pharmacology)
- Animals
- Behavior, Animal
(drug effects)
- Capsaicin
(administration & dosage)
- Disease Models, Animal
- Microdialysis
- Neuralgia
(drug therapy, physiopathology, psychology)
- Norepinephrine
(metabolism)
- Pain Threshold
(drug effects)
- Peripheral Nerve Injuries
(drug therapy, physiopathology, psychology)
- Pregabalin
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Reaction Time
(drug effects)
- Sensory System Agents
(administration & dosage)
- Spinal Nerves
(drug effects, injuries, metabolism, physiopathology)
- Time Factors
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