The indirect pathway of the nucleus accumbens shell amplifies neuropathic pain

Abstract

We examined adaptations in nucleus accumbens (NAc) neurons in mouse and rat peripheral nerve injury models of neuropathic pain. Injury selectively increased excitability of NAc shell indirect pathway spiny projection neurons (iSPNs) and altered their synaptic connectivity. Moreover, injury-induced tactile allodynia was reversed by inhibiting and exacerbated by exciting iSPNs, indicating that they not only participated in the central representation of pain, but gated activity in ascending nociceptive pathways.

The Emotional Brain as a Predictor and Amplifier of Chronic Pain

“…2A): a result consistent with evidence showing that dopamine receptor expression decreases in the NAc following an SNI injury and with a drop of dopamine concentration in the NAc after SNI injury (Ren et al 2016). More important, we observed that NAc shell indirect spiny neurons show increased excitability and decreased dendritic fields within days after SNI injury and that oral treatment with L-DOPA and naproxen blocks the effects of SNI on excitability, dendritic architecture, and synaptic connectivity and blunts neuropathic pain (Ren et al 2016).…”

“…A cellular/molecular study of NAc shell neurons revealed the mechanistic role of dopamine in the transition to chronic pain (Ren et al 2016), suggesting therapeutic potential.…”

“…Also, all drug treatments were administered by oral gavage, twice a day at assigned days, and pain behavior (unless indicated) was measured at least 12 h after gavage-that is, the morning after and just prior to the morning drug administration. Some of these data are reported in Ren et al (2016), where further experimental details are expounded.…”

Etiology and Pharmacology of Neuropathic Pain

“…In addition, tactile allodynia was reversed by inhibiting and exacerbated by exciting these neurons. This suggests that neurons in the nucleus accumbens not only participate in the central representation of pain, but that they may gate activity in ascending pathways associated with expression of neuropathic pain in higher centers (Ren et al, 2016).…”

Imaging: Show me where it hurts

“…His team has also shown that the main determinant of chronic pain is not the injury, but the properties of the person's brain, he adds. And, in rodents, the researchers have been able to block the transition from acute to chronic pain using drugs that inhibit neurons in the nucleus accumbens 7 ; a trial is under way to see if this works in humans. "I'm confident we will quickly develop a whole series of new treatment options specific for different types of chronic pain, " says Apkarian.…”