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Opioid and noradrenergic contributions of tapentadol to the inhibition of locus coeruleus neurons in the streptozotocin rat model of polyneuropathic pain
| Content Provider | Semantic Scholar |
|---|---|
| Author | Torres-Sanchez, Sonia Borges, Gisela Da Silva Micó, Juan Antonio Berrocoso, Esther |
| Copyright Year | 2018 |
| Abstract | &NA; Tapentadol is an analgesic that acts as an agonist of &mgr; opioid receptors (MOR) and that inhibits noradrenaline reuptake. Data from healthy rats show that tapentadol inhibits neuronal activity in the locus coeruleus (LC), a nucleus regulated by both the noradrenergic and opioid systems. Thus, we set out to investigate the effect of tapentadol on LC activity in streptozotocin (STZ)‐induced diabetic rats, a model of diabetic polyneuropathy, by analyzing single‐unit extracellular recordings of LC neurons. Four weeks after inducing diabetes, tapentadol dose‐response curves were obtained from animals pre‐treated with RX821002 or naloxone (alpha2‐adrenoceptors and opioid receptors antagonists, respectively). In STZ rats, the spontaneous activity of LC neurons (0.9 ± 0.1 Hz) was lower than in naïve animals (1.5 ± 0.1 Hz), and tapentadol's inhibitory effect was also weaker. Alpha2‐adrenoceptors blockade by RX821002 (100 &mgr;g/kg i.v.) in STZ animals significantly increased the spontaneous activity (from 0.8 ± 0.1 to 1.4 ± 0.2 Hz) and it dampened the inhibition of LC neurons produced by tapentadol. However, opioid receptors blockade following naloxone pre‐treatment (5 mg/kg i.v.) did not alter the spontaneous firing rate (0.9 ± 0.2 vs 0.9 ± 0.2 Hz) or the inhibitory effect of tapentadol on LC neurons in STZ animals. Thus, diabetic polyneuropathy appears to exert neuroplastic changes in LC neurotransmission, enhancing the sensitivity of alpha2‐adrenoceptors and dampening opioid receptors expression. Tapentadol's activity seems to be predominantly mediated through its noradrenergic effects rather than its influence on opioid receptors in the STZ model of diabetic polyneuropathy. HighlightsTapentadol inhibits the electrical activity of LC neurons in naïve and STZ rats.Tapentadol's inhibition on LC is weaker in STZ than in naïve rats.This inhibition is predominantly mediated by noradrenergic mechanisms in STZ rats.Opioid contribution to tapentadol's effect in the LC is low in STZ rats. |
| Starting Page | 202 |
| Ending Page | 210 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/j.neuropharm.2018.03.014 |
| PubMed reference number | 29551688 |
| Journal | Medline |
| Volume Number | 135 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/S0028390818301254 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/S0028390818301254?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/j.neuropharm.2018.03.014 |
| Journal | Neuropharmacology |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
