Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats

<p>Abstract</p> <p>Background</p> <p>Adenosine 5'-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve entrapment (SNE).</p> <p>Results</p> <p>After SNE, rats develop long-lasting decreases in ipsilateral hindpaw withdrawal thresholds to mechanical and thermal stimulation. At 15–21 days after neuropathy induction, excised ipsilateral L4-L5 DRG display significantly elevated basal extracellular ATP levels compared to contralateral or control (naive) DRG. However, KCl-evoked ATP release is no longer observed in ipsilateral DRG. We hypothesized that the differential SNE effects on basal and evoked ATP release could result from the conversion of extracellular ATP to adenosine with subsequent activation of adenosine A1 receptors (A1Rs) on DRG neurons. Adding the selective A1R agonist, 2-chloro-N⁶-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release in DRG from naïve rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further increased basal ATP levels and relieved the blockade of KCl-evoked ATP release suggesting that increased A1R activation attenuates evoked ATP release in neurons ipsilateral to SNE. To determine if altered ATP release was a consequence of altered DRG metabolism we compared O₂consumption between control and neuropathic DRG. DRG ipsilateral to SNE consumed O₂at a higher rate than control or contralateral DRG.</p> <p>Conclusion</p> <p>These data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation.</p

Spinal trigeminal neurons demonstrate an increase in responses to dural electrical stimulation in the orofacial formalin test

Primary headaches are often associated with pain in the maxillofacial region commonly classified under the term “orofacial pain” (OFP). In turn, long-lasting OFP can trigger and perpetuate headache as an independent entity, which is able to persist after the resolution of the main disorder. A close association between OFP and headache complicates their cause and effect definition and leads to misdiagnosis. The precise mechanisms underlying this phenomenon are poorly understood, partly because of the deficiency of research-related findings. We combined the animal models of OFP and headache—the orofacial formalin test and the model of trigeminovascular nociception—to investigate the neurophysiological mechanisms underlying their comorbidity. In anesthetized rats, the ongoing activity of single convergent neurons in the spinal trigeminal nucleus was recorded in parallel to their responses to the electrical stimulation of the dura mater before and after the injection of formalin into their cutaneous receptive fields. Subcutaneous formalin resulted not only in the biphasic increase in the ongoing activity, but also in an enhancement of neuronal responses to dural electrical stimulation, which had similar time profile. These results demonstrated that under tonic pain in the orofacial region a nociceptive signaling from the dura mater to convergent trigeminal neurons is significantly enhanced apparently because of the development of central sensitization; this may contribute to the comorbidity of OFP and headache

Increased Expression of Cannabinoid CB1 Receptors in Achilles Tendinosis

BACKGROUND: The endogenous cannabinoid system is involved in the control of pain. However, little is known as to the integrity of the cannabinoid system in human pain syndromes. Here we investigate the expression of the cannabinoid receptor 1 (CB₁) in human Achilles tendons from healthy volunteers and from patients with Achilles tendinosis. METHODOLOGY: Cannabinoid CB₁ receptor immunoreactivity (CB₁IR) was evaluated in formalin-fixed biopsies from individuals suffering from painful Achilles tendinosis in comparison with healthy human Achilles tendons. PRINCIPAL FINDINGS: CB₁IR was seen as a granular pattern in the tenocytes. CB₁IR was also observed in the blood vessel wall and in the perineurium of the nerve. Quantification of the immunoreactivity in tenocytes showed an increase of CB₁ receptor expression in tendinosis tissue compared to control tissue. CONCLUSION: Expression of cannabinoid receptor 1 is increased in human Achilles tendinosis suggesting that the cannabinoid system may be dysregulated in this disorder

Orofacial pain and symptoms of temporomandibular disorders in Finnish and Thai populations

Objective. Cultural or ethnic factors may play an important role in subjects’ pain reports. The aim of the study was to compare the prevalence of orofacial pain symptoms between Finnish and Thai populations. Materials and methods. The Finnish study population comprised the Northern Finland Birth Cohort 1966, of which 5696 subjects participated in the present study. The Thai sample consisted of 1501 randomly selected people living in 10 different districts in Bangkok. Data on orofacial pain was collected based on questionnaires. Results. After adjusting for age, gender and education, the logistic regression analysis showed that Thai subjects had an increased risk for reporting oral pain (OR = 4.5, 95% CI = 3.7–5.4), tooth pain (OR = 2.0, 95% CI = 1.8–2.4) and pain in the face (OR = 1.5, 95% CI = 1.2–1.7). Conclusions. It can be concluded that Thai people report more orofacial pain symptoms than Finnish subjects. Cross-cultural factors exist in the background of reporting pain symptoms in the oral and facial area

Physical, psychological and socio-demographic predictors related to patients’ self-belief of their temporomandibular disorders’ aetiology

© 2020 John Wiley & Sons LtdBackground: The aetiology of temporomandibular disorders (TMDs) has been widely discussed in literature, but little is known about patients’ self-belief of their TMD aetiology. Objective: For six categories of self-believed aetiology of the TMD complaint (viz., occlusal factors, physical trauma, emotional stress, deep pain input, parafunctions and unknown), associations with physical, psychological and socio-demographic predictors were assessed. Methods: In this retrospective study, medical records of 328 TMD patients who had visited a clinic for Orofacial Pain and Dental Sleep Medicine were analysed. Results: The most frequently reported self-believed TMD aetiology was ‘unknown’ (42.3%). The category ‘occlusal factors’ was associated with pain worsening with emotion. ‘Physical trauma’ as self-believed aetiology was associated with TMD dysfunction score. ‘Emotional stress’ was associated with awake bruxism and age 18-49 years. ‘Deep pain input’ was associated with TMD dysfunction score, sleep bruxism, and arthritis or joint pain. ‘Parafunctions’ were associated with sleep bruxism. ‘Unknown’ was associated with TMD symptoms severity and work disability. Conclusion: For each category of self-believed aetiology of the TMD complaint, different associations with physical, psychological and socio-demographic predictors were identified. This may suggest that individual phenotypes play a role in the patient's belief in the cause of the TMD complaint. Determination of phenotypic risk factors associated with aetiological self-belief might help clinicians to provide better treatment, including counselling, to their patients

Altered ATP release and metabolism in dorsal root ganglia of neuropathic rats.

BackgroundAdenosine 5'-triphosphate (ATP) has a ubiquitous role in metabolism and a major role in pain responses after tissue injury. We investigated the changes in basal and KCl-evoked ATP release from rat dorsal root ganglia (DRG) after peripheral neuropathy induction by unilateral sciatic nerve entrapment (SNE).ResultsAfter SNE, rats develop long-lasting decreases in ipsilateral hindpaw withdrawal thresholds to mechanical and thermal stimulation. At 15-21 days after neuropathy induction, excised ipsilateral L4-L5 DRG display significantly elevated basal extracellular ATP levels compared to contralateral or control (naive) DRG. However, KCl-evoked ATP release is no longer observed in ipsilateral DRG. We hypothesized that the differential SNE effects on basal and evoked ATP release could result from the conversion of extracellular ATP to adenosine with subsequent activation of adenosine A1 receptors (A1Rs) on DRG neurons. Adding the selective A1R agonist, 2-chloro-N(6)-cyclopentyladenosine (100 nM) significantly decreased basal and evoked ATP release in DRG from naïve rats, indicating functional A1R activation. In DRG ipsilateral to SNE, adding a selective A1R antagonist, 8-cyclopentyl-1,3-dipropylxanthine (30 nM), further increased basal ATP levels and relieved the blockade of KCl-evoked ATP release suggesting that increased A1R activation attenuates evoked ATP release in neurons ipsilateral to SNE. To determine if altered ATP release was a consequence of altered DRG metabolism we compared O(2) consumption between control and neuropathic DRG. DRG ipsilateral to SNE consumed O(2) at a higher rate than control or contralateral DRG.ConclusionThese data suggest that peripheral nerve entrapment increases DRG metabolism and ATP release, which in turn is modulated by increased A1R activation