Human Studies

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.

Some patients with migraine, particularly those in primary care, require effective, well-tolerated, migraine-specific oral preventive treatments.

The association between migraine and patent foramen ovale (PFO) has been documented. We aimed to investigate platelet activation, prothrombotic phenotype, and oxidative stress status of migraineurs with PFO on 100 mg/day aspirin, before and 6 months after PFO closure. Data show that, before PFO closure, expression of the classical platelet activation markers is comparable in patients and aspirin-treated healthy subjects. Conversely, MHA-PFO patients display an increased prothrombotic phenotype (higher tissue factor platelets and microvesicles and thrombin-generation potential), sustained by an altered oxidative stress status. This phenotype, which is more controlled by P2Y-blockade than by aspirin, reverted after PFO closure together with a complete migraine remission. (pLatelEts And MigRaine iN patEnt foRamen Ovale [LEARNER]; NCT03521193).

In 2015, we evaluated our practices regarding pain after breast-conserving surgery. Thereafter, we have adapted our practices by performing a systematic deep serratus plane block before the surgical incision. In 2019, we assessed the impact of these changes in terms of chronic pain. The main objective of this study was to evaluate the prevalence of chronic pain 3 months after this type of surgery.

Opioid overdose suppresses brainstem respiratory circuits, causes apnoea and may result in death. Epidural electrical stimulation (EES) at the cervical spinal cord facilitated motor activity in rodents and humans, and we hypothesized that EES of the cervical spinal cord could antagonize opioid-induced respiratory depression in humans. Eighteen patients requiring surgical access to the dorsal surface of the spinal cord between C2 and C7 received EES or sham stimulation for up to 90 s at 5 or 30 Hz during complete (OFF-State) or partial suppression (ON-State) of respiration induced by remifentanil. During the ON-State, 30 Hz EES at C4 and 5 Hz EES at C3/4 increased tidal volume and decreased the end-tidal carbon dioxide level compared to pre-stimulation control levels. EES of 5 Hz at C5 and C7 increased respiratory frequency compared to pre-stimulation control levels. In the OFF-State, 30 Hz cervical EES at C3/4 terminated apnoea and induced rhythmic breathing. In cadaveric tissue obtained from a brain bank, more neurons expressed both the neurokinin 1 receptor (NK1R) and somatostatin (SST) in the cervical spinal levels responsive to EES (C3/4, C6 and C7) compared to a region non-responsive to EES (C2). Thus, the capacity of cervical EES to oppose opioid depression of respiration may be mediated by NK1R+/SST+ neurons in the dorsal cervical spinal cord. This study provides proof of principle that cervical EES may provide a novel therapeutic approach to augment respiratory activity when the neural function of the central respiratory circuits is compromised by opioids or other pathological conditions. KEY POINTS: Epidural electrical stimulation (EES) using an implanted spinal cord stimulator (SCS) is an FDA-approved method to manage chronic pain. We tested the hypothesis that cervical EES facilitates respiration during administration of opioids in 18 human subjects who were treated with low-dose remifentanil that suppressed respiration (ON-State) or high-dose remifentanil that completely inhibited breathing (OFF-State) during the course of cervical surgery. Dorsal cervical EES of the spinal cord augmented the respiratory tidal volume or increased the respiratory frequency, and the response to EES varied as a function of the stimulation frequency (5 or 30 Hz) and the cervical level stimulated (C2-C7). Short, continuous cervical EES restored a cyclic breathing pattern (eupnoea) in the OFF-State, suggesting that cervical EES reversed the opioid-induced respiratory depression. These findings add to our understanding of respiratory pattern modulation and suggest a novel mechanism to oppose the respiratory depression caused by opioids.

It is unclear whether the electrophysiological effects of erenumab, a monoclonal antibody against the calcitonin gene-related peptide receptor, occur only at the periphery of the trigeminal system or centrally and at the cortical level.

Chronic pain conditions, including temporomandibular disorders, are closely related to poor sleep quality. This study investigated whether sleep deterioration in patients with painful temporomandibular disorder differed depending on the origin of pain, and also analyzed which clinical disease characteristics and whether psychological distress affected sleep quality. A total of 337 consecutive patients (215 women; mean age, 33.01 ± 13.01 years) with painful temporomandibular disorder (myalgia [n=120], temporomandibular joint arthralgia [n=62], mixed joint-muscle temporomandibular disorder pain [n=155]), who were assessed and classified based on the diagnostic criteria for temporomandibular disorder (DC/TMD), were enrolled. They completed a battery of standardized reports on clinical sign and symptoms, and answered questions on sleep quality, excessive daytime sleepiness, and patients' psychological status. The mean global Pittsburgh Sleep Quality Index scores were significantly higher in the mixed temporomandibular disorder pain group (6.97 ± 3.38) and myalgia group (6.40 ± 3.22) than in the arthralgia group (5.16 ± 2.94) (p=0.001). Poor sleepers were significantly more prevalent in the mixed temporomandibular disorder pain group (76.8%) and myalgia group (71.7%) than in the arthralgia group (54.8%) (p=0.006). The presence of psychological distress in the myalgia group (β=1.236, p=0.022), global severity index of the Symptom Checklist-90-Revised in the arthralgia group (β=1.668, p=0.008), and presence of headache (β=1.631, p=0.002) and self-reported sleep problems (β=2.849, p<0.001) in the mixed temporomandibular disorder pain group were associated with an increase in the Pittsburgh Sleep Quality Index score. Ultimately, as the source of pain in painful temporomandibular disorder can affect and determine sleep quality and contributing factors, and as the complex interplay between sleep and pain can vary, a comprehensive treatment approach is necessary because good sleep is required by patients.