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Sex differences in hypothalamic-mediated tonic norepinephrine release for thermal hyperalgesia in rats
M Wagner1, T Banerjee1, Y Jeong2
1The University of Michigan School of Nursing, 400 N. Ingalls Building, Ann Arbor, MI 48109, United States.
Neuroscience
|March 23, 2016
Summary
Norepinephrine (NE) is tonically released from A7 cells, activating α1-adrenoceptors to facilitate pain. This effect is amplified in neuropathic pain and involves the lateral hypothalamus differently in males and females.
Area of Science:
- Neuroscience
- Pain Research
- Pharmacology
Background:
- Neuropathic pain treatment with serotonin norepinephrine reuptake inhibitors yields variable outcomes.
- Pain facilitation via α1-adrenoceptors is implicated, but tonic norepinephrine (NE) release remains unconfirmed.
Purpose of the Study:
- To investigate tonic NE release from A7 cells after chronic constriction injury (CCI) in rats.
- To determine the role of the lateral hypothalamus (LH) in NE release in male and female rats with nociceptive and neuropathic pain.
Main Methods:
- Rats underwent CCI or remained naïve. Intrathecal administration of α1-antagonist WB4101 or α2-antagonist yohimbine was performed.
- Paw withdrawal latency (PWL) to thermal stimuli was measured.
- Synaptic transmission was blocked using cobalt chloride (CoCl) in A7 cells and the LH.
Main Results:
- WB4101 significantly increased PWL in both nociceptive and neuropathic rats, indicating α1-mediated facilitation.
- NE release from A7 cells was confirmed, with a greater effect in neuropathic pain.
- LH microinjection blocked WB4101's effect in male rats but not females, suggesting sex-specific innervation.
Conclusions:
- Tonic NE release acts on pronociceptive α1-adrenoceptors, enhancing pain, particularly after nerve injury.
- The A7 cell group is a primary source of NE, modulated by the LH.
- LH innervation of A7 cells differs between sexes, impacting pain modulation.
