Amelioration of morphine withdrawal syndrome by systemic and intranasal administration of mesenchymal stem cell-derived secretome in preclinical models of morphine dependence.

Background: Morphine is an opiate commonly used in the treatment of moderate to severe pain. However, prolonged administration can lead to physical dependence and strong withdrawal symptoms upon cessation of morphine use. These symptoms can include anxiety, irritability, increased heart rate, and muscle cramps, which strongly promote morphine use relapse.

Sex-dependent effect of inflammatory pain on negative affective states is prevented by kappa opioid receptors blockade in the nucleus accumbens shell.

Pain comorbidities include several psychological disorders, such as anxiety and anhedonia. However, the way pain affects male and female individuals and by which mechanism is not well understood. Previous research shows that pain induces alterations in the dynorphinergic pathway within the mesocorticolimbic system (MCLS), together with a relationship between corticotropin-releasing system and dynorphin release in the MCLS.

Focal mu-opioid receptor activation promotes neuroinflammation and microglial activation in the mesocorticolimbic system: Alterations induced by inflammatory pain.

Microglia participates in the modulation of pain signaling. The activation of microglia is suggested to play an important role in affective disorders that are related to a dysfunction of the mesocorticolimbic system (MCLS) and are commonly associated with chronic pain. Moreover, there is evidence that mu-opioid receptors (MORs), expressed in the MCLS, are involved in neuroinflammatory events, although the way by which they do it remains to be elucidated.