Dopamine D1 and D3 receptor modulators restore morphine analgesia and prevent opioid preference in a model of neuropathic pain.

Dopamine D1 and D3 receptor modulators restore morphine analgesia and prevent opioid preference in a model of neuropathic pain.

Publication date: May 15, 2019

A secondary consequence of spinal cord injury (SCI) is debilitating chronic neuropathic pain, which is commonly morphine resistant and inadequately managed by current treatment options. Consequently, new pain management therapies are desperately needed. We previously reported that dopamine D3 receptor (D3R) dysfunction was associated with opioid resistance and increases in D1 receptor (D1R) protein expression in the spinal cord. Here, we demonstrate that in a model of SCI neuropathic pain, adjuvant therapy with a D3R agonist (pramipexole) or D1R antagonist (SCH 39166) can restore the analgesic effects of morphine and reduce reward potential. Prior to surgery thermal and mechanical thresholds were tested in three groups of female rats (nacEFve, sham, SCI). After surgery, testing was repeated under the following drug conditions: 1) saline, 2) morphine, 3) pramipexole, 4) SCH 39166, 5) morphine + pramipexole, and 6) morphine + SCH 39166. Reward potential of morphine and both combinations was assessed using conditioned place preference. Following SCI, morphine + pramipexole and morphine + SCH 39166 significantly increased both thermal and mechanical thresholds. Morphine alone induced conditioned place preference, but when combined with either the D3R agonist or D1R antagonist preference was not induced. The data suggest that adjunct therapy with receptor-specific dopamine modulators can restore morphine analgesia and decrease reward potential and thus, represents a new target for pain management therapy after SCI.

Rodgers, H.M., Yow, J., Evans, E., Clemens, S., and Brewer, K.L. Dopamine D1 and D3 receptor modulators restore morphine analgesia and prevent opioid preference in a model of neuropathic pain. 03506. 2019 Neuroscience (406):

Concepts Keywords
Adjunct Therapy Neuroscience
Adjuvant Therapy Neuropathic pain
Agonist Ketamine
Analgesia Analgesic
Analgesic Heroin
Antagonist Morphine
Dopamine Pain
Dopamine Receptor Morphinans
Morphine RTT
Nave Euphoriants
Neuropathic Pain Opioids
Opioid Psychoactive drugs
Pain Management Drugs
Pramipexole Adjuvant therapy
Receptor Surgery
Saline Pain management
SCH Chronic neuropathic pain
Spinal Cord
Spinal Cord Injury

Semantics

Type Source Name
drug DRUGBANK Ecopipam
gene UNIPROT NF2
disease DOID SCH
drug DRUGBANK Pramipexole
pathway BSID Spinal Cord Injury
disease MESH neuropathic pain
disease DOID analgesia
drug DRUGBANK Morphine
drug DRUGBANK Dopamine

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