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Papers of the Week

Papers: 4 Jan 2020 - 10 Jan 2020

Animal Studies, Pharmacology/Drug Development

2020 04 20

Prog Neuropsychopharmacol Biol Psychiatry


Opioid receptors mRNAs expression and opioids agonist-dependent G-protein activation in the rat brain following neuropathy.


Llorca-Torralba M, Pilar-Cuéllar F, Borges G, Mico JA, Berrocoso E
Prog Neuropsychopharmacol Biol Psychiatry. 2020 04 20; 99:109857.
PMID: 31904442.


Potent opioid-based therapies are often unsuccessful in promoting satisfactory analgesia in neuropathic pain. Moreover, the side-effects associated with opioid therapy are still manifested in neuropathy-like diseases, including tolerance, abuse, addiction and hyperalgesia, although the mechanisms underlying these effects remain unclear. Studies in the spinal cord and periphery indicate that neuropathy alters the expression of mu-[MOR], delta-[DOR] or kappa-[KOR] opioid receptors, interfering with their activity. However, there is no consensus as to the supraspinal opioidergic modulation provoked by neuropathy, the structures where the sensory and affective-related pain components are processed. In this study we explored the effect of chronic constriction of the sciatic nerve over 7 and 30 days (CCI-7d and CCI-30d, respectively) on MOR, DOR and KOR mRNAs expression, using in situ hybridization, and the efficacy of G-protein stimulation by DAMGO, DPDPE and U-69593 (MOR, DOR and KOR specific agonists, respectively), using [35S]GTPγS binding, within opioid-sensitive brain structures. After CCI-7d, CCI-30d or both, opioid receptor mRNAs expression was altered throughout the brain: MOR – in the paracentral/centrolateral thalamic nuclei, ventral posteromedial thalamic nuclei, superior olivary complex, parabrachial nucleus and posterodorsal tegmental nucleus; DOR – in the somatosensory cortex [SSC], ventral tegmental area, caudate putamen [CPu], nucleus accumbens [NAcc], raphe magnus [RMg] and PB; and KOR – in the locus coeruleus. Agonist-stimulated [35S]GTPγS binding was altered following CCI: MOR – CPu and RMg; DOR – prefrontal cortex [PFC], SSC, RMg and NAcc; and KOR -PFC and SSC. Thus, this study shows that several opioidergic circuits in the brain are recruited and modified following neuropathy.