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2015 ; 35
(22
): 8442-50
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Microglia disrupt mesolimbic reward circuitry in chronic pain
#MMPMID26041913
Taylor AM
; Castonguay A
; Taylor AJ
; Murphy NP
; Ghogha A
; Cook C
; Xue L
; Olmstead MC
; De Koninck Y
; Evans CJ
; Cahill CM
J Neurosci
2015[Jun]; 35
(22
): 8442-50
PMID26041913
show ga
Chronic pain attenuates midbrain dopamine (DA) transmission, as evidenced by a
decrease in opioid-evoked DA release in the ventral striatum, suggesting that the
occurrence of chronic pain impairs reward-related behaviors. However, mechanisms
by which pain modifies DA transmission remain elusive. Using in vivo
microdialysis and microinjection of drugs into the mesolimbic DA system, we
demonstrate in mice and rats that microglial activation in the VTA compromises
not only opioid-evoked release of DA, but also other DA-stimulating drugs, such
as cocaine. Our data show that loss of stimulated extracellular DA is due to
impaired chloride homeostasis in midbrain GABAergic interneurons. Treatment with
minocycline or interfering with BDNF signaling restored chloride transport within
these neurons and recovered DA-dependent reward behavior. Our findings
demonstrate that a peripheral nerve injury causes activated microglia within
reward circuitry that result in disruption of dopaminergic signaling and reward
behavior. These results have broad implications that are not restricted to the
problem of pain, but are also relevant to affective disorders associated with
disruption of reward circuitry. Because chronic pain causes glial activation in
areas of the CNS important for mood and affect, our findings may translate to
other disorders, including anxiety and depression, that demonstrate high
comorbidity with chronic pain.
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