Chronic Pain

Pain that has no peripheral origin thought to be psychogenic can are these days treated with meds like SNRIs and anticonvulsants. 

Long term chronic pain can cause changes central nervously to perpetuate the pain.

Elimination of pain as a desirable outcome for psych remission

Afferent neurons travel to dorsal horn, fully in the spine. Many drug act here including SNRIs, and α2δ ligands acting at VSCCs (anticonv?). 

Neuropathic pain - from dmg/dysfunction to the nervous system as opposed to nociceptive conduction

Segmental central sensitization - doral horn perma responding d/t plastic changes. hyperalgesic - prolonged response to nox stim. allodynia - exaggerated response to usually innocuous stimuli

“Suprasegmental” central sensitization - happens centrally. brain turns on pain pathways w/o input. Fibromyalgia and many pain disorders of dpn, anx, especially PTSD

Things like Supraseg cen sensi MAY cause overuse and deterioration of brain matter in the DLPFC leads to the cog symptoms, mood, non-restorative sleep (fibromyalgia/fibro-fog)

Spinal μ-opioid receptors are one target of opioid analgesics; so are μ-opioid receptors in the periaqueductal gray itself

SNRIs boosts action of NE in pain since Descending NE neurons inhibit neurotransmitter release from primary afferent neurons via presynaptic α2 adrenoceptors, and inhibit activity of dorsal horn neurons via postsynaptic α2 adrenoceptors. This masks irrelevant pain and dysfunction in this and/or these neurotransmitters could help explain fibro and dpn/anx pain etc.

SNRIs include duloxetine, milnacipran, levomilnacipran, venlafaxine, desvenlafaxine, and some tricyclic antidepressants (TCAs)

Blocking VSCCs with the α2δ ligands gabapentin or pregabalin inhibits release of various neurotransmitters in the dorsal horn or in thalamus and cortex and has indeed proven to be an effective treatment for various disorders causing neuropathic pain

These meds possibly stronger in combo than alone

Problems with executive functioning in a wide variety of clinical conditions are generally linked to inefficient information processing in the dorsolateral prefrontal cortex (DLPFC) where dopamine neurotransmission is important in regulating brain circuits