Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway.

OBJECTIVE: To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms. METHODS: Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05). CONCLUSION: EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.@*METHODS@#Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).@*CONCLUSION@#EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

A Potential Objective Sign of Central Sensitization: Referred Pain Elicited by Manual Gluteus Minimus Muscle Exploration is Coincident with Pathological Autonomic Response Provoked by Noxious Stimulation.

Referred pain/sensation provoked by trigger points suits the nociplastic pain criteria. There is a debate over whether trigger points are related to a peripheral phenomenon or central sensitization (CS) processes. Referred pain is considered a possible sign of CS, which occurs probably mainly due to the abnormal activity of the immune and autonomic nervous systems. To confirm abnormal autonomic reactivity within the referred pain zone of active trigger points, a new diagnostic tool, the Skorupska Protocol® (the SP test®), was applied. The test uses noxious stimulation (10 minutes of dry needling under infrared camera control) as a diagnostic tool to confirm abnormal autonomic nervous system activity. A response to the SP test® of healthy subjects with referred pain sensations provoked by latent trigger points (LTrPs) stimulation was not explored before. The study aims at examining if LTrPs can develop an autonomic response. Methods. Two groups of healthy subjects, (i) gluteus minimus LTrPs with referred pain (n = 20) and (ii) control (n = 27), were examined using the SP test®. Results. Abnormal autonomic activity within the referred pain zone was confirmed for all analyzed LTrPs subjects. 70% of control subjects had no feature of vasodilatation and others presented minor vasomotor fluctuations. The size of vasomotor reactivity within the referred pain zone was LTrPs 11.1 + 10.96% vs. control 0.8 + 0.6% (p < 0.05). Conclusions. Noxious stimulation of latent TrPs induces abnormal autonomic nervous system activity within the referred pain zone. The observed phenomenon supports the concept of central nervous system involvement in the referred pain patomechanizm.

Proposal of a diagnostic algorithm for myofascial trigger points based on a multiple correspondence analysis of cross-sectional data.

BACKGROUND: Myofascial trigger points (MTrPS), the morphological correlate of myfascial pain syndromes (MPS), contribute to the worldwide high chronic pain burden. However, uncertainty about MTrP diagnostic criteria remains. Aim of this cross-sectional study was to characterize clusters of diagnostic criteria assessable during physical examination that might guide MTrP diagnosis. METHODS: Thirteen MTrP diagnostic criteria proposed in relevant literature were assessed by standardized examinations in the trapezius and levator scapulae muscles of 61 chronic pain patients undergoing an interdisciplinary pain assessment. Hierarchical cluster analysis from multiple correspondence analysis was applied to data of the four muscles separately. Examining physicians classified the findings as MTrP, sufficient for diagnosis of an MPS and/or relevant for the patients' pain condition. RESULTS: Taut bands, hypersensitive spots within a taut band, nodules within a taut band and referred pain (classical diagnostic criteria) were most frequent (28-66% M. trapezius, 8-21% M. levator scapulae). Restricted range of motion, pain during contraction, pain exacerbation during emotional stress, muscular weakness, jump sign, local twitch response and autonomic phenomena (complementary diagnostic criteria) occurred in 2-25% and hypersensitive spots and nodules outside of a taut band in 2-7% of the cases. Four clusters emerged: (1) no or just one diagnostic criterion, mostly a taut band alone; (2) a hypersensitive spot and/or nodule outside of a taut band partly in combination with complementary diagnostic criteria; (3) at least two classical diagnostic criteria (mostly a taut band containing a hypersensitive spot) partly in combination with complementary diagnostic criteria; (4) at least two, rather three, classical diagnostic criteria always in combination with complementary diagnostic criteria. Referred pain was specific to cluster 3 and 4. Among classical diagnostic criteria, palpable nodules within a taut band contributed least, and among complementary diagnostic criteria, restricted range of motion and pain during contraction contributed most to data representation. CONCLUSION: We propose that the definite diagnosis of an MTrP requires a hypersensitive spot potentially felt as a nodule located within a taut band in addition to either referred pain, a local twitch response or at least two complementary diagnostic criteria, whereby signs of muscular dysfunction take on greater importance.

Impact of Acetazolamide on Perioperative Pain Control in Robotic Assisted Laparoscopic Prostatectomy.

OBJECTIVE: To evaluate the efficacy of peri-operative acetazolamide for pain control in robotic assisted laparoscopic prostatectomy (RALP). Prior studies have demonstrated that preoperative acetazolamide decreased postoperative referred pain in the postsurgical period for laparoscopic procedures. The proposed mechanism is acetazolamide mediated inhibition of carbonic anhydrase, thereby preventing formation of carbonic acid and subsequent peritoneal acidosis with referred pain. This has yet to be demonstrated in the setting of RALP. METHODS AND MATERIALS: Patients undergoing RALP were randomized to receive either preoperative saline or acetazolamide prior to the procedure. Overall pain scores were recorded at multiple time points post operatively, as well as total morphine equivalents administered for adjunctive pain control. RESULTS: Thirty-one patients were included in the study: 16 patients (51.6%) received perioperative acetazolamide, and 15 patients (48.4%) received perioperative saline as placebo. Overall pain scores were similar for patients receiving acetazolamide compared to placebo at various time points: first responsive (3.5 ± 3.1 vs 4.1 ± 1.7, P = .28), immediately prior to leaving PACU (2.8 ± 2.9 vs 2.9 ± 2.9, P = .48), at 4 hours post-procedure (3.1 ± 3.0 vs 2.9 ± 1.8, P = .362), or at 24 hours post-procedure (2.3 ± 1.7 vs 2.2 ± 1.6, P = .5). Shoulder tip pain was not present in either cohort. No statistically significant difference was observed for total morphine equivalents delivered between acetazolamide and placebo (17.3 vs 20.5, P= .2, respectively). CONCLUSION: Acetazolamide does not appear to impact overall pain or shoulder tip pain in the observed cohort of patients undergoing RALP.

Low-back related leg pain: is the nerve guilty? How to differentiate the underlying pain mechanism.

Low back pain (LBP) that radiates to the leg is not always related to a lesion or a disease of the nervous system (neuropathic pain): it might be nociceptive (referred) pain. Unfortunately, patients with low-back related leg pain are often given a variety of diagnoses (e.g. 'sciatica'; 'radicular pain'; pseudoradicular pain"). This terminology causes confusion and challenges clinical reasoning. It is essential for clinicians to understand and recognize predominant pain mechanisms. This paper describes pain mechanisms related to low back-related leg pain and helps differentiate these mechanisms in practice using clinical based scenarios. We illustrate this by using two clinical scenarios including patients with the same symptoms in terms of pain localization (i.e. low-back related leg pain) but with different underlying pain mechanisms (i.e. nociceptive versus neuropathic pain).

Sensory Profiles in Patients with Low Back Pain with and Without Radiculopathy.

OBJECTIVE: During routine clinical evaluation, it can be challenging to differentiate between lumbar radiculopathy (RAD) and lower back pain with non-radicular somatic referred pain (SRP) or even axial non-radiating low back pain (LBP). The aim of this study was to characterize patients with RAD, axial LBP (aLBP), and SRP on the basis of somatosensory profiles. METHODS: Patients with LBP (n = 54) were assessed with quantitative sensory testing in the area of LBP and, in cases of RAD, additionally in the area of projecting pain. Questionnaires (PainDETECT®, EuroQol-5D, Medical Outcomes Study Sleep Scale, Hannover Functional Ability Questionnaire for Back Pain, Roland Morris Disability Questionnaire, Short Form-12 Health Survey, and Hospital Anxiety and Depression Scale) were answered by all patients. RESULTS: Patients with RAD (n = 12) had higher pain intensity scores (numeric rating scale: 5.7 ± 1.5 vs 4.1 ± 2.2; P < 0.05) and higher PainDETECT scores (14.6 ± 6.13 vs 9.7 ± 6.2; P < 0.05) than did patients with aLBP and SRP (n = 42). Patients with RAD had a more pronounced loss of small-fiber function, increased mechanical hyperalgesia, and a trend toward increased sensitivity to thermal pain in the area of LBP compared with patients with aLBP and SRP. Within patients with RAD, sensory profiles of the area of projecting pain and the area of LBP did not differ. Pressure pain hyperalgesia (measured by pressure pain threshold) and loss of mechanical detection (measured by mechanical detection threshold) in combination with the PainDETECT items numbness and prickling reached the best predictive value in detecting a radiculopathy. CONCLUSIONS: Patients with RAD demonstrated more somatosensory abnormalities than did patients with aLBP and SRP, including increased mechanical hyperalgesia and a loss of mechanical detection. The combination of pressure pain threshold, mechanical detection threshold, numbness, and prickling in the area of LBP can be a time-efficient tool to identify patients with RAD.

Phantom Limb Neuroplasticity and Maladaptive Sensory Perceptions: Why Phantom Limb Paresthesia Should Be Integrated into Referred Pain Discussions.

The concept of referred pain is an integral part of the anatomy didactic content taught and discussed in all medical school curricula.  However, this discussion has excluded the topic of phantom limb pain, despite the existence of parallels in neurophysiological explanations between these conditions. This brief viewpoint attempts to reason why phantom limb paresthesia or pain should be included in the fold of refereed pain discussions.

Prevalence and characteristics of referred pain in patients diagnosed with temporomandibular disorders according to the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) in Sharjah, United Arab Emirates.

BACKGROUND: Referred pain often complicates and delays the diagnosis of temporomandibular disorders (TMD). Elaborating the prevalence and characteristics of TMD-associated referred pain as well as the distribution of referred pain in different TMD classes will significantly improve the diagnostic process. The objectives of the present study were to assess the prevalence and to evaluate the characteristics of referred pain associated with TMD diagnosed according to the DC/TMD. METHODS: A total of 252 patients were evaluated using the DC/TMD Axes-I and -II assessment tools. Different modalities were used to treat the diagnosed TMD. Referred pain was diagnosed when the location of the perceived pain in response to palpation extended beyond the boundary of the structure that was examined. For pain locations that were perceived as deep, patients were asked to locate the surface of the area of pain. The result of the assessment was identified as positive if the patient described his perceived pain during the clinical examination as being familiar pain that was experienced in the same location in the last 30 days.  Results: TMD-associated referred pain was recorded in 153 patients (60.7%). The most common referred pain location was the temporal area (45.2%), followed by the ear (42.1%). The referred pain was recorded in disc displacement with reduction with intermittent locking and myofascial pain with referral in all patients (100%). The proportion of patients with referred pain was significantly different between the different TMD diagnostic subgroups (P < 0.001).  The recorded percentage of improvement in the referred pain following the treatment was 50.41% after 3 months and 56.65% after 6 months. CONCLUSIONS: Referred pain is a prominent feature of TMD. More studies are required with longer follow-up periods and bigger sample sizes to support the findings of the present study.

Systematic Review and Meta-Analysis of Perioperative Administration of Acetazolamide for Management of Postoperative Pain after Laparoscopy.

Background and Objective: To perform a systematic review and meta-analysis to evaluate the efficacy of perioperative acetazolamide (ACTZ) administration with laparoscopy for reducing postoperative referred pain. Methods: The following databases were searched from inception to March 1, 2020: Cochrane, PubMed, PubMed Central, Ovid, and Embase. Electronic search used: Acetazolamide AND (laparoscopy OR laparoscopic OR Celioscopy OR Celioscopies OR Peritoneoscopy OR Peritoneoscopies). No limits or filters were used. We included only studies of patients who underwent abdominal laparoscopy (LSC), had a pain assessment at approximately 24 hours postoperatively, and included a treatment with ACTZ group and a no-treatment or minimal-treatment comparison group. Results: Five studies met inclusion criteria, with a combined total of 253 participants, 116 in the ACTZ group and 137 in the control group. A Bayesian hierarchical model was assumed for the study specific treatment effects. Posterior sampling was conducted via Markov Chain Monte Carlo methods, and posterior inference carried out on the hierarchical treatment effect. ACTZ significantly decreased average pain scores compared to control group by -0.726 points (95% confidence interval -1.175-0.264). The posterior probability that ACTZ decreases mean pain scores by ≥ 0.5 was 0.846. Conclusion: Current available evidence demonstrates that perioperative ACTZ may provide a modest improvement in postoperative referred pain following LSC.

Somato-somatic theory of referred pain elucidates observations of referred sensations during micropigmentation of nipple-areolar complex in a cohort study on patients undergoing pedicled latissimus dorsi flap breast reconstruction.

AIM: Micropigmentation of the nipple-areolar complex is the final aesthetic step in autologous breast reconstruction. The mechanism of referred pain observed in patients during micropigmentation after a non-neurotonized pedicled latissimus dorsi flap breast reconstruction is poorly understood. METHODS: Patients undergoing micropigmentation for nipple-areolar restoration at our breast unit were included in this study. Baseline sensitivity of both breasts was recorded using a questionnaire and non-invasive Semmes-Weinstein monofilament testing. Patients experiencing local and regional referred symptoms, while undergoing micropigmentation, were identified and their clinical data were collected and analysed. Three months postoperatively, the patients completed a questionnaire pertaining to their satisfaction and future analgesic preference. RESULTS: Thirty (17.8%) patients experienced referred sensations during micropigmentation. Their symptoms ranged from "ache" (6.7%), "discomfort" (13.3%) to "deep pain" (13.3%) and were either local and/or referred to ipsilateral axilla, upper limb and back. The majority were pleased with postoperative outcomes [shape (30, 100%), size (28, 93.3%), colour match (22, 73.3%)] and a small number were not satisfied with the shape (2, 6.7%,) position (1, 3.3%) and appearance of the tattoo (1, 3.3%). CONCLUSION: Micropigmentation is a safe procedure with good patient satisfaction and low rates of complications; however, patients may experience significant local or referred symptoms. This observation can be explained by the proposed "somato-somatic" theory of referred pain and ascertains the need for use of oral and/or local anaesthetic as well as improved counselling in these patients.

Only cervical vertebrae C0-C2, not C3 are relevant for subgrouping migraine patients according to manual palpation and pain provocation: secondary analysis of a cohort study.

BACKGROUND: Subgrouping of migraine patients according to the pain response to manual palpation of the upper cervical spine has been recently described. Based on the neuroanatomy and the convergence of spinal and trigeminal nerves in the trigeminocervical complex, the cervical segments C1 to C3 are potentially relevant. To date it has not been investigated whether palpation results of all upper cervical segments are based on one underlying construct which allows combining the results of several tests. Therefore, the aim of this secondary analysis of a cohort study was to determine whether results from all three segments form one construct. METHODS: Seventy-one migraine patients with chronic or frequent episodic migraine diagnosed according to the international headache society classification version 3 were examined by one physiotherapist. Manual palpation using a posterior to anterior pressure was performed on the upper three cervical vertebrae unilaterally left and right. The results of the palpation according to the patients' responses were combined using factor analysis. In addition, item response theory (IRT) was used to investigate the structure of the response pattern as well as item difficulty and discrimination. FINDINGS: Factor analysis (principal component) showed that the palpation of C3 loads less onto the underlying construct than the palpation of C1 and C2. Considering a cut-off value > 1.0, the eigenvalues of all three segments do not represent one underlying construct. When excluding the results from C3, remaining items form one construct. The internal consistency of the pain response to palpation of C1 and C2 is acceptable with a Cronbach's alpha of 0.69. IRT analysis showed that the rating scale model fits best to the pain response pattern. The discrimination value (1.24) was equal for all items. Item difficulty showed a clear hierarchical structure between the palpation of C1 and C2, indicating that people with a higher impairment are more likely to respond with referred pain during palpation of C2. CONCLUSION: Statistical analysis confirms that results from the palpation of the cervical segments C1 and C2 in migraine patients can be combined. IRT analysis confirmed the ordinal pattern of the pain response and showed the higher probability of a pain response during palpation of C2. The pain response to C3 palpation is not relevant for unidimensional IRT analysis. TRIAL REGISTRATION: German registry of clinical trials (DRKS00015995), Registered 20. December 2018, https://www.drks.de/drks_web/setLocale_EN.do.

Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia.

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling.

Effectiveness of Transcranial Direct Current Stimulation Combined With Exercising in People With Fibromyalgia: A Randomized Sham-Controlled Clinical Trial.

OBJECTIVE: To evaluate the effectiveness of transcranial direct current stimulation (tDCS) combined with exercising in people with fibromyalgia. DESIGN: Randomized, triple-blind, sham-controlled, clinical trial. SETTING: Primary health care center. PARTICIPANTS: A total of 120 volunteer participants (N=120) between 18 and 65 years old and diagnosed with fibromyalgia. Four participants dropped out of the study for causes unrelated to the intervention. INTERVENTION: Participants were randomized into 3 groups (active tDCS+exercising, sham tDCS+exercising, no-intervention control). The intervention was delivered in 5 sessions over 2 weeks. MAIN OUTCOME MEASURES: Pain intensity and referred pain area after suprathreshold pressure stimulation. RESULTS: Pain intensity further decreased in the active tDCS group vs control (mean, -14.43; 95% confidence interval, -25.27 to -3.58) at post intervention, unlike the sham tDCS group. Both tDCS groups did not achieve greater reductions in referred pain vs control. In the active tDCS group, health status (mean, -14.80; 95% confidence interval, -23.10 to -6.50) and pain catastrophizing (mean, -6.68, 95% confidence interval, -11.62 to -1.73) improved at post intervention, and so did health status (mean, -8.81; 95% confidence interval, -17.11 to -0.51), pain catastrophizing (mean, -7.00; 95% confidence interval, -12.13 to -1.87), and depression (mean, -3.52; 95% confidence interval, -6.86 to -0.19) after 1 month. In the sham tDCS group, improvements were recorded in health status (mean, -13.21; 95% confidence interval, -21.52 to -4.91) and depression (mean, -3.35; 95% confidence interval, -6.35 to -0.35) at post intervention and in health status (mean, -8.77; 95% confidence interval, -17.06 to -0.47), pain catastrophizing (mean, -5.68; 95% confidence interval, -10.80 to -0.55), and depression (mean, -3.98; 95% confidence interval, -7.31 to -0.64) after 1 month. No intergroup differences were observed between active and sham tDCS. CONCLUSIONS: Active and sham tDCS improved health status, pain catastrophizing, and depression vs control, but pain intensity decreased only in the active tDCS group.

The correlation between scapulocostal syndrome and masticatory myofascial pain on selected pain and functional parameters- an observational study.

OBJECTIVES: Although scapulocostal syndrome (SCS) and masticatory myofascial pain (MMP) occur in different regions, the concept of myofascial linkage and neurophysiology may be proven per the connection of the two disorders. Therefore, this study aimed to investigate the correlation between SCS and MMP on selected pain and functional parameters. METHOD: 75 participants with SCS participated in the protocol. The diagnosis of SCS was considered by the presence of muscle referred pain in the medial scapular muscles. All participants were measured for pain intensity, pressure pain threshold (PPT), and craniovertebral angle (CV-angle) for pain and functional parameters related to SCS. They were measured for pain intensity, PPT, and mouth distance for the pain and functional parameters related to MMP. The diagnosis of MMP was considered by the presence of muscle tenderness of the masticatory muscle and the decreasing of mouth opening distance. The correlation between SCS and MMP was determined using Pearson's correlation coefficient and Spearman's correlation. RESULTS: Participants exhibiting SCS were diagnosed for MMP at 74.67%. The results showed positive correlations in pain intensity and PPT between SCS and MMP (r = 0.367, r = 0.478, p < 0.01), PPT of SCS, and mouth distance amid both pain-free and maximum mouth opening conditions, respectively (r = 0.290, r = 0.282, p < 0.05). CONCLUSION: In conclusion, SCS and MMP present an association with each other in terms of both selected pain, and functional parameters. Thus, a treatment program for SCS patients should be concerned with the masticatory muscles even if they did not report any pain at the jaw area.

Standardized palpation of the temporalis muscle evoke referred pain and sensations in individuals without TMD.

OBJECTIVES: This study aimed to determine if standardized palpations of the temporalis muscle evoke referred pain and/or sensations in individuals without TMD. MATERIALS AND METHODS: This was a randomized, single-blinded study. The mechanical sensitivity of the right temporalis muscle was assessed in 32 participants without TMD with nine different stimulations to 15 test sites using palpometers (different stimulus intensities (0.5, 1.0, and 2.0 kg) and durations (2, 5, and 10 s). After each stimulus, participants were asked to score perceived pain intensity and intensity of unpleasantness on a 0-100 numeric rating scale as an indicator of mechanical sensitivity in the temporalis muscle and to indicate any areas of referred pain/sensations on a body chart. RESULTS: Pain intensity significantly differed between palpation durations, intensities, and test sites (P < 0.001). In contrast, unpleasantness significantly differed between palparation duration and intensities (P < 0.001), but not test sites. Participants more frequently reported referred pain/sensations evoked by the 10-s (34.4%) as opposed to the 2-s (6.3%) and 5-s (15.6%) palpation duration at the 2.0-kg stimulus intensity (P < 0.05). CONCLUSIONS: Our present results indicate that referred pain/sensations in the orofacial region can be evoked by standardized palpation of the temporalis muscle and influenced by the palpation duration in individuals without TMD. CLINICAL RELEVANCE: Referred pain/sensations from the temporalis muscle were duration- and intensity-dependent processes originating from local stimuli.

We Should Pay Attention to "Referred Pain" - A Case of Acute Myocardial Infarction That Masked and Delayed the Diagnosis of Esophageal Perforation.

We herein report a 93-year-old woman diagnosed with acute myocardial infarction (AMI) based on typical laboratory findings of severe chest pain accompanied by throat pain. This condition was initially interpreted as referred pain of cardiac origin. However, the patient had persistent throat pain after successful percutaneous coronary intervention. Upper esophageal perforation with life-threatening acute mediastinitis was unexpectedly identified by a further examination. Clinicians should have a high index of suspicion in cases with persistent symptoms thought to be referred pain among AMI patients, as these symptoms may not be of cardiac origin but rather a sign of another concomitant critical disease.

Referred Somatic Hyperalgesia Mediates Cardiac Regulation by the Activation of Sympathetic Nerves in a Rat Model of Myocardial Ischemia / 神经科学通报·英文版

Myocardial ischemia (MI) causes somatic referred pain and sympathetic hyperactivity, and the role of sensory inputs from referred areas in cardiac function and sympathetic hyperactivity remain unclear. Here, in a rat model, we showed that MI not only led to referred mechanical hypersensitivity on the forelimbs and upper back, but also elicited sympathetic sprouting in the skin of the referred area and C8-T6 dorsal root ganglia, and increased cardiac sympathetic tone, indicating sympathetic-sensory coupling. Moreover, intensifying referred hyperalgesic inputs with noxious mechanical, thermal, and electro-stimulation (ES) of the forearm augmented sympathetic hyperactivity and regulated cardiac function, whereas deafferentation of the left brachial plexus diminished sympathoexcitation. Intradermal injection of the α2 adrenoceptor (α2AR) antagonist yohimbine and agonist dexmedetomidine in the forearm attenuated the cardiac adjustment by ES. Overall, these findings suggest that sensory inputs from the referred pain area contribute to cardiac functional adjustment via peripheral α2AR-mediated sympathetic-sensory coupling.

Referred Orofacial Pain as an Initial Symptom of Distant, Nonmetastatic Cancer: Report of a Case and Review of the Literature.

Referred orofacial pain as the first symptom of an otherwise silent distant, nonmetastatic cancer has been reported, but there is sparse literature on the subject. Referred pain may not be considered in the orofacial pain differential diagnosis because of its rarity; however, this may delay a cancer diagnosis. The authors present a case report and a review of the English literature. Peer-reviewed publications were identified through a systematic search of MEDLINE, Embase, and Cochrane CENTRAL. Historic cases were reviewed, and available data regarding demographics, pain characteristics, treatment, cancer diagnosis, and outcome were extracted. Thirty-seven cases were identified. All cancers were intrathoracic. The average age was 54.1 years with a slight female predominance (3:2). Common pain characteristics were (1) diffuse location affecting the ear (76%), jaw (46%), and temple (30%); (2) constant duration (65%); (3) aching quality (74%); (4) severe intensity (94%); and (5) associated systemic symptoms (68%) such as weight loss and digital clubbing. The average time from the onset of facial pain to seeking medical attention was 9 months, and the average time from seeking medication attention to cancer diagnosis was 8 months. Orofacial pain was often attributed to odontogenic (35%) or neuropathic (25%) causes, and treatments for these conditions were also common. The impact of referred orofacial pain on the cancer prognosis was not possible because of the nature of the reviewed studies (case reports with no comparison group). Cancer-associated referred orofacial pain as a first symptom is rare but should be considered in cases with intractable pain and associated systemic symptoms.