Transcranial and Transcutaneous Stimulation for Pain: What Have We Learned From the COVID-19 Pandemic Shutdown?

BACKGROUND: Transcranial magnetic stimulation (TMS) and transcutaneous magnetic stimulation (tMS) offer a novel noninvasive treatment option for chronic pain. While the recent COVID-19 pandemic caused by the SARS-CoV-2 virus resulted in a temporary interruption of the treatments for patients, it provided an excellent opportunity to assess the long-term sustainability of the treatment, and the feasibility of resuming the treatments after a brief period of interruption as no such data are available in current literature. METHODS: First, a list of patients whose pain/headache conditions have been stably controlled with either treatment for at least 6 months prior to the 3-month pandemic-related shutdown was generated. Those who returned for treatments after the shutdown were identified and their underlying pain diagnoses, pre- and posttreatment Mechanical Visual Analog Scale (M-VAS) pain scores, 3-item Pain, Enjoyment, and General Activity (PEG-3), and Patient Health Questionnaire-9 scores were assessed in 3 phases: Phase I (P1) consisted of a 6-month pre-COVID-19 period in which pain conditions were stably managed with either treatment modality; Phase II (P2) consisted of the first treatment visit period immediately after COVID-19 shutdown; and Phase III (P3) consisted of a 3-4 month post-COVID-19 shutdown period patients received up to 3 sessions of either treatment modality after the P2 treatment. RESULTS: For pre- and posttreatment M-VAS pain scores, mixed-effect analyses for both treatment groups demonstrated significant (P < 0.01) time interactions across all phases. For pretreatment M-VAS pain scores, TMS (n = 27) between-phase analyses indicated a significant (F = 13.572, P = 0.002) increase from 37.7 ± 27.6 at P1 to 49.6 ± 25.9 at P2, which then decreased significantly (F = 12.752, P = 0.001) back to an average score of 37.1 ± 24.7 at P3. Similarly, tMS (n = 25) between-phase analyses indicated the mean pretreatment pain score (mean ± standard deviation [SD]) increased significantly (F = 13.383, P = 0.003) from 34.9 ± 25.1 at P1 to 56.3 ± 27.0 at P2, which then decreased significantly (F = 5.464, P = 0.027) back to an average score of 41.9 ± 26.4 at P3. For posttreatment pain scores, the TMS group between-phase analysis indicated the mean posttreatment pain score (mean ± SD) increased significantly (F = 14.206, P = 0.002) from 25.6 ± 22.9 at P1 to 36.2 ± 23.4 at P2, which then significantly decreased (F = 16.063, P < 0.001) back to an average score of 23.2 ± 21.3 at P3. The tMS group between-phase analysis indicates a significant (F = 8.324, P = 0.012) interaction between P1 and P2 only with the mean posttreatment pain score (mean ± SD) increased from 24.9 ± 25.7 at P1 to 36.9 ± 26.7 at P2. The combined PEG-3 score between-phase analyses demonstrated similar significant (P < 0.001) changes across the phases in both treatment groups. CONCLUSIONS: Both TMS and tMS treatment interruptions resulted in an increase of pain/headache severity and interference of quality of life and functions. However, the pain/headache symptoms, patients' quality of life, or function can quickly be improved once the maintenance treatments were restarted.

Pain paths among post-COVID-19 condition subjects: A prospective cross-sectional study with in-person evaluation.

BACKGROUND: New-onset chronic pain has been acknowledged as part of the post-COVID-19 condition. However, available fine-grained data about its clinical phenotype, trajectories and main associated characteristics remain scarce. We described the distinct temporal evolutions of post-COVID-19 pain and their epidemiological and phenotypical features. METHODS: A prospective cross-sectional study enrolled post-COVID-19 condition patients (i.e. who had persisting COVID-19-related symptoms over 30 days since their first positive laboratory test), whose COVID-19 diagnosis had been supported by RT-PCR of oral/nasopharyngeal swab or serology. They underwent in-person evaluations with a structured interview, pain and quality-of-life-related questionnaires and thorough physical examination. Chronic pain (CP) and probable neuropathic pain (NP) were defined according to IASP criteria. RESULTS: The present study included 226 individuals, 177 (78.3%) of whom presented over 3 months since their first COVID-19 symptom. New-onset pain occurred in 170 (75.2%) participants and was chronic in 116 (68.2%). A chronic course was associated with COVID-19-related hospitalization, new-onset fatigue, lower cognitive performance, motor and thermal sensory deficits, mood and sleep impairments and overall lower quality-of-life levels. Probable NP occurred in only 7.6% new-onset pain patients, and was associated with pain chronification, new-onset fatigue, motor and thermal sensory deficits, mechanical allodynia and lower rates of SARS-CoV-2 vaccination. Previous CP was reported by 86 (38.1%) individuals and had aggravated after the infection in 66 (76.7%) of them, which was associated with orthostatic hypotension. CONCLUSIONS: Post-COVID pain phenomena follow different paths, which are associated with specific clinical and epidemiological features, and possibly distinct underlying mechanisms, prognostic and therapeutic implications. SIGNIFICANCE: COVID-19-related pain usually follows a chronic course and is non-neuropathic. Its possible courses and phenotypes are associated with distinct clinical and epidemiological features. This suggests differing underlying mechanisms, which may have significant prognostic and therapeutic implications.

Chronic pain in post-COVID syndrome.

Our body senses two types of pain, acute and chronic. Acute pain lasts for a short time. It occurs when our body wants to protect us from a dangerous situation. This way, our nerves are telling us that something is wrong. But if some time passes since our injury, treatment or surgery and the pain or discomfort persists, we are speaking of chronic pain. It is often difficult to determine its intensity or even prove its existence. The discomfort and pain are not relieved and physical pain may be accompanied by mental issues. At present, during the COVID-19 pandemic, chronic pain is becoming more prominent, and it is also associated with the post-COVID syndrome. In their efforts to help patients suffering from COVID-19, many new treatment protocols have been prepared and various antiviral drugs and other potentially useful drugs have been used (often without prior approval or testing). Basically, it was a kind of 'experimental' treatment. At present, thanks to quick therapy decisions and as part of COVID-19 prevention, we have succeeded in stabilising the situation all over the world. A relatively fast development of vaccines against SARS-CoV-2 with a view to achieve collective immunity has greatly contributed to this. On the other hand, 'quick decisions' have contributed to other significant issues which we are beginning to deal with now, i.e, in the effort to defeat the virus, many experts regarded the adverse effects of the medications used to be of secondary importance. In the article we would like to point out the other side of the 'successful' treatment of COVID-19, namely the possible iatrogenic conditions which significantly contribute to the post-COVID­19 syndrome and chronic pain. The importance of preventive measures over uncertain result of COVID-19 treatment is emphasised (Tab. 4, Fig. 1, Ref. 50). Text in PDF www.elis.sk Keywords: iatrogenic conditions; chronic pain; co-morbidity; pain syndrome; pandemic; post-COVID­19 syndrome.

[COVID-19 and chronic pain: online survey in the domestic population]. / Covid-19 és krónikus fájdalom: online felmérés a pandémia alatt fájdalommal élo, ellátásban nem részesülo személyek körében.

Background and purpose: The problems caused by the COVID-19 epidemic have the worst impact on chronic patient populations. People with chronic pain are one of the most vulnerable groups due to stress, disruption of daily routine, family problems, illness and difficulty in hospital care. It is therefore essential to assess the situation and mental well-being of this group. The aim of this survey was to assess chronic pain patients during the COVID-19 pandemic, addressing psychological background factors that might affect pain symptoms, such as depression, emotion regulation, alexithymia, well-being, health literacy and social support. Methods: 158 people participated in the survey, reporting pain for at least 3 months but had not received medical treatment. Data was collected at two dates: February and December 2021. Participants completed an online questionnaire due to the pandemic situation. The following six psychological questionnaires were used in the survey: Toronto Alexithymia Scale, Beck Depression Inventory 9-item version, Difficulty in Emotion Regulation Scale, Multidimensional Scale of Perceived Social Support, Chew-questions measuring health literacy, WHO Well-being Index. Results: The participants ranged from 20 to 80 years in age, of whom 140 (88%) were female. 42 participants (27%) achieved severe alexithymia. 118 people (75%) had depression, of which 72 people (46%) had mild depression, 26 (16%) had moderate depression, and 20 (13%) had severe depression. The degree of pain and alexithy-mia (r(158) = 0.16, p = 0.004), depression (r(158) = 0.41, p < 0.001), difficulties in emotion regulation (r(158) = 0.26, p = 0.004), and health literacy, and difficulties in emotion regulation (r(158) = 0.25, p = 0.001) were positively and significantly related. Conclusion: In addition to the characteristic comorbidities of people living with pain (e.g. anxiety, emotion disorder, sleep disorder), the epidemic-induced prolonged social isolation, stress and fear of illness may explain the proportion of high depression, emotion regulation difficulties or health literacy problems in the study sample which exacerbate alexithymia and the degree of pain. Based on these results it is important to draw the attention of professionals to the appropriate health care and educational needs of those affected.

Substance use and common contributors to morbidity: A genetics perspective.

Excessive substance use and substance use disorders (SUDs) are common, serious and relapsing medical conditions. They frequently co-occur with other diseases that are leading contributors to disability worldwide. While heavy substance use may potentiate the course of some of these illnesses, there is accumulating evidence suggesting common genetic architectures. In this narrative review, we focus on four heritable medical conditions - cardiometabolic disease, chronic pain, depression and COVID-19, which are commonly overlapping with, but not necessarily a direct consequence of, SUDs. We find persuasive evidence of underlying genetic liability that predisposes to both SUDs and chronic pain, depression, and COVID-19. For cardiometabolic disease, there is greater support for a potential causal influence of problematic substance use. Our review encourages de-stigmatization of SUDs and the assessment of substance use in clinical settings. We assert that identifying shared pathways of risk has high translational potential, allowing tailoring of treatments for multiple medical conditions. FUNDING: SSR acknowledges T29KT0526, T32IR5226 and DP1DA054394; RLK acknowledges AA028292; AA acknowledges DA054869 & K02DA032573. The funders had no role in the conceptualization or writing of the paper.

Decrypting the cellular and molecular intricacies associated with COVID-19-induced chronic pain.

Pain is one of the clinical manifestations that can vary from mild to severe symptoms in COVID-19 patients. Pain symptoms can be initiated by direct viral damage to the tissue or by indirect tissue injury followed by nociceptor sensitization. The most common types of pain that are reported to occur in COVID-19 patients are headache, myalgia, and chest pain. With more and more cases coming in the hospitals, many new and unique symptoms of pain are being reported. Testicular and abdominal pain are rare cases of pain that are also being reported and are associated with COVID-19. The SARS-CoV-2 virus has a high affinity for angiotensin-converting enzyme-2 receptor (ACE-2) which acts as an entry point for the virus. ACE-2/ Ang II/AT 1 receptor also participates directly in the transmission of pain signals from the dorsal horn of the spinal cord. It induces a series of complicated responses in the human body. Among which the cytokinetic storm and hypercoagulation are the most prominent pathways that mediate the sensitization of sensory neurons facilitating pain. The elevated immune response is also responsible for the activation of inflammatory lipid mediators such as COX-1 and COX-2 enzymes for the synthesis of prostaglandins (PGs). PG molecules especially PGE2 and PGD2 are involved in the pain transmission and are found to be elevated in COVID-19 patients. Though arachidonic acid pathway is one of the lesser discussed topics in COVID-19 pathophysiology, still it can be useful for explaining the unique and rarer symptoms of pain seen in COVID-19 patients. Understanding different pain pathways is very crucial for the management of pain and can help healthcare systems to end the current pandemic situation. We herein review the role of various molecules involved in the pain pathology of COVID-19.

The COVID-19 pandemic and its consequences for chronic pain: a narrative review.

The COVID-19 pandemic transformed everyday life, but the implications were most impactful for vulnerable populations, including patients with chronic pain. Moreover, persistent pain is increasingly recognised as a key manifestation of long COVID. This narrative review explores the consequences of the COVID-19 pandemic for chronic pain. Publications were identified related to the COVID-19 pandemic influence on the burden of chronic pain, development of new-onset pain because of long COVID with proposed mechanisms and COVID-19 vaccines and pain interventions. Broadly, mechanisms underlying pain due to SARS-CoV-2 infection could be caused by 'systemic inflammatory-immune mechanisms', 'direct neuropathic mechanisms' or 'secondary mechanisms due to the viral infection or treatment'. Existing chronic pain populations were variably impacted and social determinants of health appeared to influence the degree of effect. SARS-CoV-2 infection increased the absolute numbers of patients with pain and headache. In the acute phase, headache as a presenting symptom predicted a milder course. New-onset chronic pain was reportedly common and likely involves multiple mechanisms; however, its prevalence decreases over time and symptoms appear to fluctuate. Patients requiring intensive support were particularly susceptible to long COVID symptoms. Some evidence suggests steroid exposure (often used for pain interventions) may affect vaccine efficacy, but there is no evidence of clinical repercussions to date. Although existing chronic pain management could help with symptomatic relief, there is a need to advance research focusing on mechanism-based treatments within the domain of multidisciplinary care.

Cancer pain during an epidemic and a pandemic.

PURPOSE OF REVIEW: As our global population ages, cancer has become more prevalent. Thankfully, oncologic treatments are highly effective, leading to significantly improved rates of long-term survival. However, many of these therapies are associated with persistent pain syndromes. Clinicians caring for people with cancer must understand how the influence of the current epidemic of opioid misuse and the coronavirus disease 2019 (COVID-19) pandemic have complicated cancer pain management. Creative solutions can emerge from this knowledge. RECENT FINDINGS: Persistent pain due to cancer and its treatment can be managed through multimodal care, although efforts to mitigate the opioid misuse epidemic have created challenges in access to appropriate treatment. Isolation measures associated with the COVID-19 pandemic have limited access to nonpharmacologic therapies, such as physical therapy, and have exacerbated mental health disorders, including anxiety and depression. SUMMARY: Cancer pain treatment requires more nuanced assessment and treatment decisions as patients live longer. Societal factors multiply existing challenges to cancer pain relief. Research is needed to support safe and effective therapies.

Music Modulates Awake Bruxism in Chronic Painful Temporomandibular Disorders.

OBJECTIVE: In this experimental study, we aimed to determine whether guided music listening (GML) - a music intervention based on models of mood mediation and attention modulation - modulates masticatory muscle activity and awake bruxism in subjects with chronic painful muscular temporomandibular disorders (TMD myalgia, mTMD), a condition causing a significant burden to patients, their families, and healthcare systems. BACKGROUND: Awake bruxism - a stress behavior characterized by clenching of the teeth - is a strong contributor to chronic mTMD. GML modulates psychological stress and motor responses and could thus reduce muscle activity in chronic musculoskeletal conditions, including mTMD. METHODS: We recorded the electromyographic (EMG) activity in the right masseter of 14 women with chronic (>6 months) mTMD (median [IQR] = 39.5.3 [24.3] years) and 15 pain-free women (median [IQR] = 30.0 [3.5] years) during a GML session, including 3 music (stressful, relaxing, and participants' favorite music) and a no-music (pink noise) control blocks, each lasting 15 minutes. We measured the motor effort of the right masseter relative to the participants' maximum voluntary contraction (MVC), the muscular effort to maintain mandibular posture (EMGposture ), and to produce spontaneous awake bruxism episodes (EMGbruxism ), and the duration and frequency of spontaneous awake bruxism episodes. We tested between-group and within-group (between blocks) differences, as well as the effect of the interaction group by experimental block on these outcome measures. RESULTS: In both groups, EMGposture was significantly affected by the interaction group by experimental block (P < .001). Compared to pink noise [mean (95% CI); mTMD: 2.2 (1.6-2.8) %MVC; Controls: 1.1 (0.5-1.7) %MVC], EMGposture increased during the stressful music block [contrast estimate (95% CI); mTMD: +0.8 (0.7-0.8) %MVC; Controls: +0.3 (0.3-0.4) %MVC; both P < .001], and decreased during the relaxing [mTMD: -0.4 (-0.5 to -0.4) %MVC; Controls: -0.3 (-0.4 to -0.3) %MVC; both P < .001] and favorite [mTMD: -0.5 (-0.6 to -0.5) %MVC; Controls: -0.5 (-0.5 to -0.4) %MVC; both P < .001] music blocks. EMGposture was greater in mTMD individuals than controls during the favorite music [contrast estimate (95% CI): +1.1 (0.2-1.9) %MVC; P = .019] and the pink noise [+1.1 (0.2-2.0) %MVC; P = .014] blocks. EMGbruxism was significantly affected by the interaction group by experimental block (P < .001). In mTMD participants, compared to the pink noise block [mean (95% CI); 23.8 (16.0-31.6) %MVC], EMGbruxism increased during the stressful music block [contrast estimate (95% CI); +10.2 (8.6-11.8) %MVC], and decreased during the relaxing [-6.2 (-8.1 to -4.3) %MVC; P < .001] and favorite [-10.2 (-12.2 to -9.1) %MVC; P < .001] music blocks. These effects were not observed in the control group [mean (95% CI); pink noise: 19.3 (10.9-27.6); stressful: 21.2 (12.9-29.4) %MVC; relaxing: 21.6 (13.3-29.9) %MVC; favorite: 24.2 (15.8-32.7) %MVC; all P > .05]. EMGbruxism was significantly greater in mTMD participants than controls during the stressful music block [contrast estimate (95% CI): +12.9 (1.6-24.2) %MVC; P = .026). GML did not affect the duration or the frequency of awake bruxism in either group (median [IQR], mTMD: 23.5 [96.7] s, range 1-1300 seconds; Controls: 5.5 [22.5], range 0-246 seconds; P = .108). The frequency of awake bruxism episodes was greater in the mTMD group compared to controls only during the pink noise block (median [IQR], mTMD: 5 [15.3] episodes, range 0-62 episodes; Controls: 1 [3] episode, range 0-27 episodes; P = .046). No significant between-group differences were found in either the overall time spent engaging in awake bruxism (median [IQR], mTMD: 23.5 [96.7] s, range 1-1300 seconds; Controls: 5.5 [22.5], range 0-246 seconds; P = .108), or during each block (all P > .05). CONCLUSIONS: In subjects with chronic mTMD, relaxing music and the individual's favorite music decreased the muscular effort during spontaneous awake bruxism episodes by 26% and 44% (relative changes), respectively. In contrast, stressful music increases it by about 43%. Because of its positive effects on awake bruxism, GML with selected music could be a promising and non-invasive component of a multimodal approach for the management of chronic mTMD.

Pain experience and social support of endometriosis patients during the COVID-19 pandemic in Germany - results of a web-based cross-sectional survey.

BACKGROUND: Endometriosis is a chronic pain condition in premenopausal women. Pain is mainly characterized by pain intensity and may induce disability in all areas of daily life. Nevertheless, pain is influenced by emotional and social factors as well. Social distancing measures or quarantine, as reaction to rapidly rising infections with the COVID-19 virus due to the SARS-CoV-2 pandemic, were implemented across Europe to prevent the spread of the virus and social distancing measures were imposed by the German government by beginning of March 2020 with initiation of the lockdown by the end of March 2020. The objective of this study was to assess, how social distancing measures during the lockdown impacted the various aspects of pain perception in a group of chronic pain patients, such as women suffering from endometriosis. METHODS: Between 6th to 27th April 2020, an online questionnaire was activated at internet platforms of endometriosis patients support groups. Participants were asked retrospectively at one time point about their visual pain intensity measured by the visual analogue scale (VAS) and pain disability via pain disability index (PDI) prior to initiation of social distancing measures in Germany (VASP, PDIP), as well as the pain intensity and pain disability since implementation of social distancing measures (VASI, PDII). Differences of VAS and PDI previous and after implementation of social distancing measures were displayed as ΔVAS and ΔPDI. Pain experience and social support were assessed by a 5-point Likert scale. RESULTS: 285 participants completed at least one question regarding pain intensity, disability, pain experience or social support. Dysmenorrhea, the symptom with the highest level of pain assessed by VAS, decreased significantly during the SARS-CoV-2 pandemic compared to the time period prior to social isolation (45.30% respondents experienced improvemenet vs 40.50% who experienced worsening; p = 0.025). The global physical impairment improved significantly (improvement of pain induced disability in 48.20% vs 40.90% with worsening of pain symptoms; p = 0.032) after the implementation of social distancing measures. Pain experience was negatively affected by social distancing measures, since frequency of pain awareness increased in 43.6% (p<0.001) of participants and 30.0% (p<0.001) more participants experienced pain as a threat. Verbalization of pain experience was reduced in 36.6% (p = 0.001) of participants and 14.6% (p = 0.91), 21.9% (p<0.001) and 31.5% (p<0.001) of participants reported less social support from their partner, family and friends. CONCLUSIONS: Physical pain and disability on one hand and emotional and social pain experience on the other were differentially affected by the emerged emotional, social and health care constraints related to the SARS-CoV-2 pandemic.