Is there a way for a nonaddictive opioid for endometriosis pain?

Endometriosis pain is related to a multitasking neuronal network but opioid receptors play a huge role.

Key Points

Highlights:

• Opioid receptors play a role in endometriosis pain and a well-designed nonaddictive combination drug is warranted.

Importance:

• The review explains the role of internal opioid receptors on pain perception and the hypothalamic axis and possible therapeutic options.

What's done here:                                       

• The pathways for endometriosis pain production and the possible receptors taking part in that network have been explained.
• Possible roles of opioid drugs and the modifications that should be applied to overcome side effects and addiction have been described as future study plans.

Key Results:

• Locally, nociceptors are activated in and around the endometriotic lesions, which convert the stimulus into action potentials which are transmitted via the spinal cord to the brain to cause pain perception.
• Endometriosis-related pain is due to inflammation-related pain mediator release, nerve infiltration, or compression and when the somatosensory nervous system is affected, named neuropathic pain.
• The endogenous opioid system, particularly in the reproductive system, plays an important role in neurogenic inflammation and pain and has an impact on the control of emotional and cognitive responses.
• Out of different receptor types, the micro opioid receptor is expressed in the human endometrium and endometriotic lesions and its expression pattern differs by progesterone use in endometriosis patients and during the menstrual cycle.
• Nociceptin orphanin peptide receptors have a high distribution within the immune system, and their activation produces anti-hyperalgesia and anti-allodynic effects in chronic pain.
•  The opioid receptors take a role in all steps of the hypothalamic hypophysis axis and overconsumption of opioids results in as hypogonadotropic hypogonadism.
• In 2021 a new trial has been announced for a non-opioid therapy option (an agonist) that offers a strong analgesic effect without the side effects commonly associated with opioids but not been proven yet.

Limitations:

• The field for finding an opioid drug without an addiction and side effect risk will be a promising non-hormonal treatment option but the literature is still restricted.

Lay Summary

Endometriosis is a neuro-inflammatory disease whose current medical treatment is hormonal therapy. Given the side effects and the possible interactions between the opioid system and pain mechanisms, a new opioid medication might be promising.

in the review conducted by Dr.Mechsner et al., the literature has been analyzed for the effects of the opioid system on endometriosis-related pain and the possible suggestions for new drug production.

The analysis showed, locally, nociceptors are activated in and around the endometriotic lesions, which convert the stimulus into action potentials that are transmitted via the spinal cord to the brain and cause pain perception.

Endometriosis-related pain is due to inflammation-related pain mediator release, nerve infiltration, or compression and when the somatosensory nervous system is affected it is named neuropathic pain. The endogenous opioid system particularly in the reproductive system plays an important role in neurogenic inflammation and pain and its implications in the control of emotional and cognitive responses.

Out of different receptor types, the micro-opioid receptor is expressed in the human endometrium and endometriotic lesions and their expression pattern differs by progesterone use in endometriosis patients and during the menstrual cycle. Nociceptin orphanin peptide receptors have a high distribution within the immune system, and their activation produces anti-hyperalgesia and anti-allodynic effects in chronic pain. The opioid receptors take a role in all steps of the hypothalamic hypophyseal axis and the overconsumption of opioids results in hypogonadotropic hypogonadism.

In 2021 a new trial has been announced for a non-opioid therapy option, a Nociceptin orphanin peptide agonist that offers a strong analgesic effect without the side effects commonly associated with opioids but not proven yet. The authors concluded that the field for finding an opioid drug without an addiction and side effect risk will be a promising non-hormonal treatment option while the possible candidates are "Nociceptin orphanin peptide" or "micro-opioid receptors" the literature is still restricted.

Research Source: https://pubmed.ncbi.nlm.nih.gov/36675147/