The association of chronic pain with depression is becoming increasingly recognized.
Treating both the conditions together is essential for an effective treatment outcome. In this regard,
it is important to identify a shared mechanism involved in the association of chronic pain with depression.
Central serotonin (5-hydroxytryptamine; 5-HT) neurotransmission has long been known
to participate in the processing of signals related to pain. It also plays a key role in the pathogenesis
and treatment of depression. Although functional responses to serotonin are mediated via the activation
of multiple receptor types and subtypes, the 5-HT1A subtype is involved in the processing of
nociception as well as the pathogenesis and treatment of depression. This receptor is located presynaptically,
as an autoreceptor, on the perikaryon and dendritic spines of serotonin-containing
neurons. It is also expressed as a heteroreceptor on neurons receiving input from serotonergic neurons.
This article targets the 5-HT1A receptors to show that indiscriminate activation of pre and
postsynaptic 5-HT1A receptors is likely to produce no therapeutic benefits; biased activation of the
5-HT heteroreceptors may be a useful strategy for treating chronic pain and depression individually
as well as in a comorbid condition.
Keywords: Chronic pain, depression, serotonin, 5-HT1A receptor, heteroreceptors, autoreceptors.
Abdallah, C.G.; Geha, P. Chronic pain and chronic stress: two sides of the same coin? Chronic Stress , 2017, 1, 1-10.
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