Clinical study of tongue pain: Serum zinc, vitamin B12, folic acid, and copper concentrations, and systemic disease

Yoshida, Hiroaki; Tsuji, Kaname; Sakata, Takeichi; Nakagawa, Akihito; Morita, Shosuke

doi:10.1016/j.bjoms.2009.08.001

Cited by 9 publications

(6 citation statements)

References 10 publications

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“…The lack of zinc effects in mutant mice unequivocally demonstrates that binding of high-affinity Zn 2+ to NR2A subunit is essential for zinc-induced analgesia. These results provide a molecular mechanism for the pain-relieving properties of dietary zinc and strengthen the notion that zinc therapy may successfully treat intractable pain, such as fibromyalgia 36 , peripheral neuropathy 37 or other pain abnormalities 38 . The zinc phenotype of mutant mice also reveals a largely unanticipated key role of NR2A-containing receptors in pain processing.…”

Section: Resultssupporting

confidence: 65%

Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit

et al. 2011

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Zinc is abundant in the central nervous system and regulates pain, but the underlying mechanisms are unknown. In vitro studies have shown that extracellular zinc modulates a plethora of signaling membrane proteins, including NMDA receptors containing the NR2A subunit, which display exquisite zinc sensitivity. We created NR2A-H128S knock-in mice to investigate whether Zn2+–NR2A interaction influences pain control. In these mice, high-affinity (nanomolar) zinc inhibition of NMDA currents was lost in the hippocampus and spinal cord. Knock-in mice showed hypersensitivity to radiant heat and capsaicin, and developed enhanced allodynia in inflammatory and neuropathic pain models. Furthermore, zinc-induced analgesia was completely abolished under both acute and chronic pain conditions. Our data establish that zinc is an endogenous modulator of excitatory neurotransmission in vivo and identify a new mechanism in pain processing that relies on NR2A NMDA receptors. The study also potentially provides a molecular basis for the pain-relieving effects of dietary zinc supplementation.

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Section: Resultssupporting

confidence: 65%

Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit

et al. 2011

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“…The fact that thyroid hormones play an important role in muscle function [26] is supported by the common occurrence of neuromuscular symptoms [27] and musculoskeletal disorders [28] in patients with thyroid dysfunctions. Thyroid disease has also previously been associated with idiopathic tongue pain in a clinical study [29]. Observed levels of PTH in the present study may possibly reflect some prevalence of parathyroid disturbances or disturbances in the hormonal thyroid-regulating pathways in the TMD group.…”

Section: Discussionsupporting

confidence: 56%

Serum Analysis in Patients with Temporomandibular Disorders: A Controlled Cross-Sectional Study in Norway

Staniszewski

Lygre

Berge

et al. 2019

Pain Research and Management

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Temporomandibular disorder (TMD) is characterized by pain and dysfunction in the temporomandibular join (TMJ) and the masticatory apparatus. Associations with autoimmune diseases, inflammatory conditions, and nutrition deficiencies have been reported in previous studies of TMD patients. To evaluate essential proteins, hormones, electrolytes, and vitamins in serum from TMD patients, a standard blood sample analysis was performed in 60 TMD patients and 60 healthy controls matched for age and gender, retrieving 19 different analyses. We found that TMD patients had significantly higher values of hemoglobin (p=0.036), cobalamin (p=0.023), albumin (p=0.005), parathyroid hormone (PTH) (p=0.038), and vitamin D (p=0.005), and significantly lower values of creatinine (p=0.006) and potassium (p=0.011), compared to controls. In the TMD group, most of the determinants had a wider range, and several subjects, compared to the control group, had values outside the normal reference area. However, most of the TMD patients and controls had values within normal biological range. Our findings could not associate any severe systemic disease, malnutrition, or systemic inflammation with the TMD. Results from our study suggest that serum analyses should neither be used as a biomarker of TMD nor a diagnostic tool for an individual subject with TMD.

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“…The μ-type of opioid receptors-mediated effects has the most important contribution to addiction development [ 100 ]. Apparently in disagreement with the effect of zinc of lowering opioids biological effects by decreasing their binding affinity to receptors (evidenced by in vitro studies) are the evidences from animal experiments showing a positive correlation between the activity of endogenous opioids system and zinc levels [ 72 , 86 ].…”

Section: Discussionmentioning

confidence: 99%

“…A clinical study revealed the association between low plasma zinc and tongue pain, a type of neuropathic pain [ 86 ]. Zinc levels in patients with trichodynia, a condition associating pain and a stinging sensation of the scalp related to diffuse alopecia, are not different compared to controls [ 87 ].…”

Section: Zinc Ions Actions and Zinc Deficit Effects On Models Of Painmentioning

confidence: 99%

Zinc involvement in opioid addiction and analgesia – should zinc supplementation be recommended for opioid-treated persons?

Ciubotariu

Ghiciuc

Lupușoru

2015

Subst Abuse Treat Prev Policy

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IntroductionZinc chelators were shown to facilitate some opioid-withdrawal signs in animals. Zinc deficiency, which affects more than 15 % the world’s population, is also common among opioid consumers and opioid-treated animals exhibit misbalances of zinc distribution.AimThe present study focuses on how zinc ions interfere with opioid dependence/addiction and analgesia, trying to preliminary discuss if zinc supplementation in opioid-users should be recommended in order to reduce the risk of addiction.MethodsAll relevant literature was searched up to April 2015. The search was performed using the term “zinc” plus combinations of following terms: “opioid receptors”, “opioid” or representatives of this class, “addiction”, “dependence”, “analgesia”, and “pain”. Human, animal, in vitro studies and reviews were including.ResultsBoth human and animal studies revealed decreased serum zinc under opioid-administration conditions, attributed mainly to increased urinary elimination (humans) or redistribution (animals). Moreover, animal studies revealed decreased brain zinc levels in morphine-treated animals, with increased zinc hepatic levels, but also an enhancement of endogenous opioid system activity and a possible reduction of morphine withdrawal by zinc. In vitro studies revealed reduction of opioid ligands binding to receptors by zinc. However, the very few in vivo animal studies on opioid analgesia revealed controversial results, as zinc demonstrated clear analgesic effect, but zinc associated to opioids doesn’t result in a potentiation of the analgesic effect.ConclusionZinc dietary supplementation in patients treated with opioids for cancer-related chronic pain should be considered, due to the high incidence of zinc deficiency, also well-documented in opioid consumers. The low toxicity of orally-administered zinc also pleads for this idea. The main contra-argument to zinc administration in opioid-treated persons is related to the way zinc influences opioid-induced analgesia.

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Clinical study of tongue pain: Serum zinc, vitamin B12, folic acid, and copper concentrations, and systemic disease

Cited by 9 publications

References 10 publications

Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit

Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit

Serum Analysis in Patients with Temporomandibular Disorders: A Controlled Cross-Sectional Study in Norway

Zinc involvement in opioid addiction and analgesia – should zinc supplementation be recommended for opioid-treated persons?

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