Promising biomedical subcutaneous delivery system in opioid disaccustom process: In vitro/in vivo evaluation of naloxone microparticles on antagonist effect of morphine.

The addiction induced by the misuse of opioids, is not only a public health emergency but also a social and economic welfare. The main therapy is based on opioid antagonists. Oral and injectable naltrexone administration is the most widely used, presenting some inconveniences: poor patient adherence to the oral daily dosing schedule, cases of hepatitis and clinically significant liver dysfunction. This study proposes the in vitro e in vivo evaluation of anti-opioid properties of naloxone loaded-poly(lactic-co-glycolic) acid microparticles (NX-MP). In previous studies, NX-MP showed in vitro sustained naloxone release for one week at least. Our results demonstrate the in vitro efficacy of the NX-MP antagonizing for 7 days the morphine effect in SH-SY5Y cells and myenteric plexus-longitudinal muscle preparations isolated from guinea-pig ileum. The in vivo evaluation of the NX-MP was carried out in mice testing the antagonism of the antinociceptive effect of morphine. Results showed that subcutaneous administration of NX-MP blocked the morphine effect. The results of this work suggest that the subcutaneous administration of NX-MP enhances naloxone therapeutic efficacy as non-addictive medication and could be a promising alternative to naltrexone. Furthermore, the dose of NX-MP can be adapted to the patient necessities. It would be an interesting advantage to treat opioid-addiction.

Characterization of the nociceptive effect of carrageenan: Masseter versus gastrocnemius.

INTRODUCTION: To better understand the pathophysiology of chronic muscle pain, there are multiple animal models that mimic different acute/chronic pain conditions, such as carrageenan injection. Our previous studies demonstrated differences between muscles of different innervation in acute pain. In this study we characterized the effect of carrageenan in 2 muscles: masseter (trigeminal innervation) and gastrocnemius (spinal innervation). METHODS: Carrageenan (3%, 6%, and 9%) was injected into the masseter and gastrocnemius of rats. Mechanical, heat, and chemical nociceptive thresholds were measured for 14 days. RESULTS: Carrageenan did not induce mechanical allodynia or thermal hypersensitivity in either muscle. Instead, it induced a short-lasting mechanical hyperalgesia, greater in the masseter than in the gastrocnemius. CONCLUSION: Carrageenan injected into the masseter and gastrocnemius induces a short-lasting hyperalgesia. These results could indicate a higher susceptibility of orofacial muscles to this type of insult and, consequently, a difference between trigeminal and spinal innervation. Muscle Nerve 56: 804-813, 2017.

Role of cannabinoids in the management of neuropathic pain.

The treatment of pain, particularly neuropathic pain, is one of the therapeutic applications of cannabis and cannabinoids that is currently under investigation and that stimulates interest among clinicians and basic researchers. Animal pain models, including models of acute, antinociceptive, inflammatory and neuropathic pain, have demonstrated the antinociceptive efficacy of cannabinoids without causing serious alterations in animal behaviour. These data, together with the historic and current empiric use of cannabinoids, support the interest in the analysis of their effectiveness in treating neuropathic pain. The evaluation of controlled trials that focus on the effect of cannabinoids on neuropathic pain reveals that this class of drugs is able to significantly reduce pain perception. Nevertheless, this effect is generally weak and clinical relevance remains under evaluation. Moreover, there is a lack of controlled trials and, in particular, comparisons with other drugs generally used in the treatment of neuropathic pain. Despite the fact that further research is required to achieve a definitive assessment, current data obtained from basic research and from analysis of the available controlled trials indicate that cannabinoids can be accepted as a useful option in the treatment of neuropathic pain.