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Related Experiment Video

Updated: Jan 20, 2026

Demonstration of Cutaneous Allodynia in Association with Chronic Pelvic Pain
06:44

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Published on: June 23, 2009

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µ-Opioid Activity in Chronic TMD Pain Is Associated with COMT Polymorphism.

T D Nascimento1, N Yang1, D Salman1

  • 1Headache and Orofacial Pain Effort (H.O.P.E.), Biologic and Materials Sciences Department, University of Michigan School of Dentistry, Ann Arbor, MI, USA.

Journal of Dental Research
|September 7, 2019
PubMed
Summary

Chronic temporomandibular disorder (TMD) patients show reduced endogenous opioid receptor activity during pain, particularly those with specific COMT gene variations. This suggests genetic factors influence pain sensitivity and opioid system function in TMD.

Keywords:
chronic painfacial paingeneticsgenotypeneuroimagingpositron emission tomography

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Area of Science:

  • Neuroscience
  • Genetics
  • Pain Research

Background:

  • Chronic pain management presents a dilemma regarding opioid versus nonopioid analgesics.
  • The impact of chronic pain on the endogenous opioid system and genetic influences remain unclear.
  • Catechol-O-methyltransferase (COMT) polymorphisms are investigated for their role in pain modulation.

Purpose of the Study:

  • To investigate the endogenous µ-opioid system's activation in chronic temporomandibular disorder (TMD) patients.
  • To determine the influence of COMT gene polymorphisms on µ-opioid receptor (µOR) binding potential during pain.

Main Methods:

  • Positron emission tomography (PET) with [11C]carfentanil was used to measure µOR nondisplaceable binding potential (BPND).
  • Scans were performed on 12 chronic TMD patients and 12 healthy controls (HCs) at rest and during a masseteric pain challenge.
  • Participants were genotyped for COMT alleles.

Main Results:

  • No significant differences in resting-state µOR BPND were observed between TMD patients and HCs.
  • During pain challenge, TMD patients showed significantly reduced µOR BPND in the parahippocampus compared to HCs (P = 0.002).
  • Reduced µOR BPND correlated with longer pain chronicity in TMD patients (P < 0.001).
  • TMD patients with the COMT Val158Met polymorphism exhibited higher pain sensitivity and chronicity, with altered µOR BPND.
  • TMD diagnosis, COMT genotype, and pain chronicity explained 52% of µOR BPND variance in the parahippocampus.

Conclusions:

  • Strong evidence suggests dysregulation of the endogenous opioid and limbic systems in chronic TMD.
  • COMT genotype influences pain sensitivity and opioid system function in TMD patients.
  • Findings support precision medicine approaches for identifying TMD patients susceptible to chronic pain and opioid dysfunction based on genetic profiles.