OPRM1 A118G (rs1799971): Pain, Pleasure & Reward

The OPRM1 gene encodes the mu-opioid receptor, a key player in pain perception, reward, and social bonding. The A118G variant (rs1799971) affects receptor function in ways that influence pain sensitivity, response to opioid medications, addiction vulnerability, and even how you experience social connection. Understanding this variant has practical implications for pain management and addiction awareness.

What is OPRM1 A118G?

The mu-opioid receptor is the primary target for both endogenous opioids (endorphins) and exogenous opioids (morphine, codeine, etc.). It mediates:

• Pain relief (analgesia)
• Reward and pleasure responses
• Physical dependence and addiction potential
• Social bonding (endorphins are released during positive social interactions)

The A118G variant causes an amino acid substitution (asparagine to aspartate) at position 40, which affects receptor binding and expression.

Understanding Your Genotype

• AA (A/A): Wild type; typical mu-opioid receptor function
• AG (A/G): Heterozygous; intermediate receptor function
• GG (G/G): Variant; reduced receptor expression and altered binding affinity

How A118G Affects Pain and Reward

Pain Sensitivity

The G allele is associated with:

• Higher pain sensitivity in experimental studies
• Lower pain threshold and tolerance
• Potentially higher opioid requirements for adequate pain control
• May need higher doses of morphine after surgery

Response to Opioid Medications

This variant has important pharmacogenetic implications:

• G allele carriers may require 30-50% higher opioid doses for equivalent pain relief
• May have different side effect profiles
• Relevant for post-surgical pain management
• May affect response to medications like naltrexone used in addiction treatment

Addiction Risk

The relationship with addiction is complex:

• G allele associated with stronger hedonic response to alcohol in some studies
• May predict better response to naltrexone treatment for alcoholism
• Some studies show G allele associated with increased opioid addiction risk
• Findings are population-specific and not entirely consistent

Social Bonding and Pleasure

The endogenous opioid system plays a role in social reward:

• G allele may be associated with reduced pleasure from social bonding
• Some research links G allele to higher sensitivity to social rejection
• May influence attachment styles and relationship behavior

Prevalence

• European ancestry: G allele frequency approximately 15-20%
• East Asian populations: Higher frequency - 40-50% G allele
• African ancestry: Lower frequency - approximately 1-5%
• Hispanic populations: Approximately 15-20%

Practical Implications

Pain Management Considerations

• If you carry the G allele and require surgery, informing your anesthesiologist about your genotype may help optimize pain management
• Non-opioid pain management strategies may be particularly valuable
• Multi-modal approaches combining different pain relief mechanisms

Addiction Awareness

• Be aware of potential increased vulnerability (though not deterministic)
• If seeking treatment for alcohol use disorder, naltrexone may be particularly effective for G allele carriers
• Extra caution with opioid prescriptions

Supporting Natural Endorphins

Regardless of genotype, supporting your natural opioid system is beneficial:

• Exercise: Powerful endorphin release (the "runner's high")
• Social connection: Positive interactions release endorphins
• Laughter: Genuine laughter increases endorphins
• Music: Can stimulate endorphin release
• Dark chocolate: Contains compounds that affect endorphin signaling
• Spicy foods: Capsaicin triggers endorphin release

Testing with NutraHacker

Understanding your OPRM1 status provides insight into pain response tendencies and reward processing. NutraHacker analyzes this variant along with other genes affecting pain, mood, and addiction vulnerability.

Frequently Asked Questions

Should I refuse opioid pain medication if I have the G allele?

No. The variant affects dosing needs, not safety. If opioids are medically indicated, work with your healthcare provider to find appropriate dosing. The information suggests you may need different amounts for adequate relief, not that opioids are contraindicated.

Does this mean I'll become addicted to opioids?

No genetic variant determines addiction. While the G allele may influence reward response, addiction involves many factors including environment, mental health, stress, and choice. Being aware of potential vulnerability can inform cautious decision-making.

How does this interact with COMT?

COMT affects dopamine breakdown while OPRM1 affects opioid signaling - both contribute to reward and pain processing. Individuals with both low COMT activity (Met/Met) and the OPRM1 G allele may have a particular pain sensitivity profile. NutraHacker reports analyze these interactions.

References

1. Bond C, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters beta-endorphin binding and activity. PNAS. 1998;95(16):9608-9613.
2. Chou WY, et al. Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology. 2006;105(2):334-337.
3. Anton RF, et al. An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence. Arch Gen Psychiatry. 2008;65(2):135-144.