Found on the membrane of nerve cells, mu opioid receptors acts as a ‘middle-man’ to opioid analgesia, opioid tolerance and addiction. The Mu Opioid Receptor, often referred to as MOR, plays a important role in addiction process. As a member of the opioid receptor family, it is primarily found in the brain and spinal cord. To put it simply, this receptor is responsible for the effects of opioid drugs, both prescribed and illicit, on your body.

When opioids attach to the Mu Opioid Receptor, they activate a chain of events that result in pain relief, sedation and even feelings of euphoria. This provides an explanation for why opioids can be highly addictive. Over time, your body becomes dependent on these opioids and cravings for the drugs can become overpowering.

Understanding the Mu Opioid Receptor is fundamental for addiction treatment. Medications like methadone, buprenorphine and naloxone are used to target this receptor, helping to manage withdrawal symptoms and reduce cravings. By blocking the Mu Opioid Receptor, these medications can aid in the recovery process by alleviating discomfort and reducing the risk of relapse.

The Mu Opioid Receptor is not a recent discovery. It was identified and characterised back in the 1970s. Since then, scientists have continued to study this receptor to gain a better understanding of its function and develop more effective treatments for addiction.

Tolerance and Physical Dependence

Physical dependence can develop after 2 to 10 days of continuous opioid use with abrupt cessation leading to withdrawal syndrome. This syndrome, as per the ICD-10, is a group of symptoms emerging from the withdrawal of a substance after prolonged or high-dose use. Withdrawal symptoms include physiological disturbances and clinical manifestations like pain, autonomic symptoms (diarrhea, rhinorrhea, diaphoresis), central nervous system effects (sleeplessness, restlessness, tremors) and strong medication cravings. Addiction, a potential outcome of drug dependence, is marked by psychological and behavioural symptoms, including compulsive use and a high tendency to relapse after withdrawal.

Tolerance mechanisms show that high doses of opioids can lead to MOR (and DOR) internalization, necessitating greater opioid intake for the same effect due to fewer receptors. When opioids are removed (e.g., using an antagonist), the endogenous opioids fail to activate the remaining receptors.

Opioid therapy using MOR agonists raises concerns due to the potential for developing tolerance and physical dependence. Tolerance occurs when consistent stimulation of the MORs requires increasingly higher doses to achieve the same effect. In cancer patients receiving pain treatment, this tolerance is often due to escalating pain levels rather than the drugs themselves. Understanding the mechanisms behind tolerance and dependence is fundamental for managing opioid therapy effectively and developing new treatments. Research, including in vitro mutagenesis and receptor chimera analysis, focuses on specific domains and amino acid residues of the MOR to understand its function better.

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