Involvement of the Lateral Amygdala in the Antiallodynic and Reinforcing Effects of Heroin in Rats after Peripheral Nerve Injury

• Published in: Anesthesiology (Philadelphia) 2011-03, Vol.114 (3), p.633-642
• Main Authors: MARTIN, Thomas J, BUECHLER, Nancy L, KIM, Susy A, EWAN, Eric E, RUOYU XIAO, CHILDERS, Steven R
• Format: Article
• Language: English
• Subjects: Amygdala - physiology; Analgesics, Opioid - pharmacology; Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Conditioning, Operant - drug effects; Enkephalin, Ala-MePhe-Gly- - pharmacology; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Heroin - pharmacology; Hyperalgesia - drug therapy; Hyperalgesia - psychology; Infusions, Intravenous; Male; Medical sciences; Naltrexone - analogs & derivatives; Naltrexone - pharmacology; Narcotic Antagonists - pharmacology; Peripheral Nerve Injuries; Rats; Rats, Inbred F344; Reinforcement, Psychology; Self Administration; Spinal Nerves - injuries
• ISSN: 0003-3022; 1528-1175
• DOI: 10.1097/aln.0b013e318209aba7

Neuropathic pain alters opioid self-administration in rats. The brain regions altered in the presence of neuropathic pain mediating these differences have not been identified, but likely involve ascending pain pathways interacting with the limbic system. The amygdala is a brain region that integrates noxious stimulation with limbic activity. μ-Opioid receptors were blocked in the amygdala using the irreversible antagonist, β-funaltrexamine, and the antiallodynic and reinforcing effects of heroin were determined in spinal nerve-ligated rats. In addition, the effect of β-funaltrexamine was determined on heroin self-administration in sham-operated rats. β-Funaltrexamine decreased functional activity of μ-opioid receptors by 60 ± 5% (mean ± SD). Irreversible inhibition of μ-opioid receptors in the amygdala significantly attenuated the ability of doses of heroin up to 100 μg/kg to reverse hypersensitivity after spinal nerve ligation. Heroin intake by self-administration in spinal nerve-ligated rats was increased from 5.0 ± 0.3 to 9.9 ± 2.1 infusions/h after administration of 2.5 nmol of β-funaltrexamine in the lateral amygdala, while having no effect in sham-operated animals (5.8 ± 1.6 before, 6.7 ± 0.9 after). The antiallodynic effects of 60 μg/kg heroin were decreased up to 4 days, but self-administration was affected for up to 14 days. μ-Opioid receptors in the lateral amygdala partially meditate heroin's antiallodynic effects and self-administration after peripheral nerve injury. The lack of effect of β-funaltrexamine on heroin self-administration in sham-operated subjects suggests that opioids maintain self-administration through a distinct mechanism in the presence of pain.