In the spinal cord, chronic pain can dramatically increase PACAP neurotransmitter levels (top panel, green fluorescent signal with arrows) on the affected side compared to the normal control side. The neurotransmitter signal travels in a neurocircuit that reaches the amygdala in the brain which controls stress-related behaviors (bottom panel, green area in cartoon denotes amygdala region).
New studies show increased expression of PACAP – a peptide neurotransmitter the body releases in response to stress – is also increased in response to neuropathic pain and contributes to these symptoms. The researchers examined the expression of PACAP (pituitary adenylate cyclase activating polypeptide) along one of the nervous system’s pathways to the brain – the spino-parabrachiomygdaloid tract – which travels from the spinal cord to the amygdala, the brain’s home base for emotional behavior.
Using models for chronic pain and anxiety, as well as models that can trace PACAP neurocircuits, the team members were able to observe where the stress and chronic pain pathways intersected. “Chronic pain and anxiety-related disorders frequently go hand-in-hand,” says Victor May, Ph.D., professor of neurological sciences at the University of Vermont (UVM). In a 2011 study, he and members of the research team found that PACAP was highly expressed in women exhibiting PTSD symptoms.
PACAP and CRH immunoreactivities are differentially distributed and regulated in the CeA. Tissue sections from control (A) and chronically stressed (B) rats were examined for CeA PACAP (Cy2, green) and CRH (Cy3, red) staining patterns. In both groups, CeA fiber PACAP immunoreactivity was predominantly in the lateral capsular region (CeLC) with diffuse staining extending into the lateral division (CeL); CRH immunoreactivity was localized predominantly to the CeL. From quantitative image analyses, only CRH immunoreactivity was augmented by chronic variate stress (C, n = 3). These results complemented quantitative PCR measurements which also demonstrated increased CRH transcript expression after stress (D, n = 6). Data represent mean ∀ SEM. Asterisk, significantly different from control at p < 0.05. Scale bar, 250 :m
While May and his colleagues saw an increase in anxiety-related behaviors in models of chronic pain, the anxious behavior and pain hypersensitivity were significantly reduced when a PACAP receptor antagonist was applied.
“By targeting this regulator and pathway, we have opportunities to block both chronic pain and anxiety disorders,” says May, whose next step is to work with University of Vermont chemistry colleagues to develop small molecule compounds that can antagonize PACAP actions. “This would be a completely different approach to using benzodiazepine and opioids – it’s another tool in the arsenal to battle chronic pain and stress-related behavioral disorders.” http://www.uvm.edu/medicine/?Page=news&storyID=23304&category=spot1
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322675/
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