A Functional Magnetic Resonance Imaging Study on Activation of Anterior Cingulate Cortex at Episode and Interictal Phases in Migraine

<sec> <title>Objective:</title> By using amplitude of low-frequency fluctuations (ALFF) we have analyzed activationsin brain regions at different phases in migraineurs. </sec> <sec> <title>Methods:</title> Participants included 41 patients with migraine, 19 in episode and 22 in interictal phase, and 22 controls in the healthy condition. To analyze the brain function of patients and controls, ALFF was used for performing the post-processing in the resting state by scores of Montreal Cognitive Assessment (MoCA) scale, Mini-Mental State Examination (MMSE), Hamilton Anxiety Rating Scale (HAM-A) and Hamilton Depression Rating Scale (HAM-D). </sec> <sec> <title>Results:</title> The comparison between groups of patients with migraine in the episode or interictal phases, and healthy controls showed that both episode and interictal migraine groups had the similar HAM-A and HAM-D scores (P > 0.05), but higher than that in controls (P < 0.01). For ALFF values of Episode and Interictal groups, the Montreal Neurological Institute (MNI) coordinates of the decreased ALFF were (−9, 42, 9), the voxel size = 215, including the bilateral anterior cingulate cortex (ACC), T =−4.15, without significant differences. Patients in Interictal group were with a stronger activation at MNI coordinates (12, 51, 12), in the bilateral ACC, voxel size = 90, T =3.87. </sec> <sec> <title>Conclusion:</title> ACC plays an adaptive, regulatory role in migraine and is related to multiple brain regions, which may mediate activation through descending anti-nociceptive pathways. ACC is related to opioid receptor and glutamate excitatory regulation. </sec>

Acid-sensing ion channels modulate bladder nociception

Our study indicates that protons and their cognate acid-sensing ion channel receptors are part of a mechanism that operates at bladder afferent terminals to control their function and that the loss of this regulatory mechanism results in hyperactivation of nociceptive pathways and the development of pain in the setting of chemical-induced cystitis.

Combined Neurophysiologic and Neuroimaging Approach to Reveal the Structure-Function Paradox in Cervical Myelopathy

Objective:To explore the so-called “structure-function paradox” in individuals with focal spinal lesions by means of tract-specific MRI coupled with multi-modal evoked potentials and quantitative sensory testing.Methods:Individuals with signs and symptoms attributable to cervical myelopathy (i.e., no evidence of competing neurological diagnosis) were recruited in the Balgrist University Hospital, Zurich, Switzerland between February 2018 and March 2019. We evaluated the relationship between the extent of structural damage within spinal nociceptive pathways (i.e., dorsal horn, spinothalamic tract, anterior commissure) assessed with atlas-based MRI , and 1) the functional integrity of spinal nociceptive pathways measured with contact heat-, cold-, and pinprick- evoked potentials and 2) clinical somatosensory phenotypes assessed with quantitative sensory testing.Results:Sixteen individuals (mean age 61 years) with either degenerative (N=13) or post-traumatic (N=3) cervical myelopathy participated in the study. Most individuals presented with mild myelopathy (modified Japanese Orthopaedic Association score (mJOA)>15; N=13). 71% of individuals presented with structural damage within spinal nociceptive pathways on MRI. Yet, 50% of these individuals presented with complete functional sparing (i.e., normal contact heat-, cold-, and pinprick- evoked potentials). The extent of structural damage within spinal nociceptive pathways was neither associated with functional integrity of thermal (heat: p=0.57; cold: p=0.49) and mechano-nociceptive pathways (p=0.83) nor with the clinical somatosensory phenotype (heat: p=0.16; cold: p=0.37; mechanical: p=0.73). The amount of structural damage to the spinothalamic tract did not correlate with spinothalamic conduction velocity (p>0.05; rho=-0.11).Conclusions:Our findings provide neurophysiological evidence to substantiate that structural damage in the spinal cord does not equate to functional somatosensory deficits. This study recognizes the pronounced structure-function paradox in cervical myelopathies and underlines the inevitable need for a multi-modal phenotyping approach to reveal the eloquence of lesions within somatosensory pathways.

Long-term effects of early pain and injury

Nociceptive pathways are functional following birth, and acute responses to noxious stimuli have been documented from early in development in clinical and laboratory studies. The ability of noxious afferent input to alter the level of sensitivity of nociceptive pathways in the adult nervous system, with, for example, the development of central sensitization, is well established. However, the developing nervous system has additional susceptibilities to alterations in neural activity, and pain in early life may produce effects not seen following the same input at older ages. As a result, early tissue injury may lead to persistent changes in somatosensory processing and altered sensitivity to future noxious stimuli. Furthermore, there is increasing evidence that neonatal pain can result in long-term changes in cognitive and affective behavior. Effects of pain in early life are superimposed on a highly plastic developing system, and long-term outcomes vary depending on the type and severity of the injury, and on the evaluation methods used. Laboratory studies allow evaluation of different injuries, potential confounding factors, underlying mechanisms, and potential analgesic modulation.

Microstructural plasticity in nociceptive pathways after spinal cord injury

ObjectiveTo track the interplay between (micro-) structural changes along the trajectories of nociceptive pathways and its relation to the presence and intensity of neuropathic pain (NP) after spinal cord injury (SCI).MethodsA quantitative neuroimaging approach employing a multiparametric mapping protocol was used, providing indirect measures of myelination (via contrasts such as magnetisation transfer (MT) saturation, longitudinal relaxation (R1)) and iron content (via effective transverse relaxation rate (R2*)) was used to track microstructural changes within nociceptive pathways. In order to characterise concurrent changes along the entire neuroaxis, a combined brain and spinal cord template embedded in the statistical parametric mapping framework was used. Multivariate source-based morphometry was performed to identify naturally grouped patterns of structural variation between individuals with and without NP after SCI.ResultsIn individuals with NP, lower R1 and MT values are evident in the primary motor cortex and dorsolateral prefrontal cortex, while increases in R2* are evident in the cervical cord, periaqueductal grey (PAG), thalamus and anterior cingulate cortex when compared with pain-free individuals. Lower R1 values in the PAG and greater R2* values in the cervical cord are associated with NP intensity.ConclusionsThe degree of microstructural changes across ascending and descending nociceptive pathways is critically implicated in the maintenance of NP. Tracking maladaptive plasticity unravels the intimate relationships between neurodegenerative and compensatory processes in NP states and may facilitate patient monitoring during therapeutic trials related to pain and neuroregeneration.

New Trends in Pharmacological Treatments for Osteoarthritis

Osteoarthritis (OA) is the leading cause of function loss and disability among the elderly, with significant burden on the individual and society. It is a severe disease for its high disability rates, morbidity, costs, and increased mortality. Multifactorial etiologies contribute to the occurrence and development of OA. The heterogeneous condition poses a challenge for the development of effective treatment for OA; however, emerging treatments are promising to bring benefits for OA management in the future. This narrative review will discuss recent developments of agents for the treatment of OA, including potential disease-modifying osteoarthritis drugs (DMOADs) and novel therapeutics for pain relief. This review will focus more on drugs that have been in clinical trials, as well as attractive drugs with potential applications in preclinical research. In the past few years, it has been realized that a complex interaction of multifactorial mechanisms is involved in the pathophysiology of OA. The authors believe there is no miracle therapeutic strategy fitting for all patients. OA phenotyping would be helpful for therapy selection. A variety of potential therapeutics targeting inflammation mechanisms, cellular senescence, cartilage metabolism, subchondral bone remodeling, and the peripheral nociceptive pathways are expected to reshape the landscape of OA treatment over the next few years. Precise randomized controlled trials (RCTs) are expected to identify the safety and efficacy of novel therapies targeting specific mechanisms in OA patients with specific phenotypes.

Opioid-free anaesthesia for the surgical correction of abnormalities associated with brachycephalic obstructive airway syndrome in five dogs

Opioid-free anaesthesia is currently becoming more popular in human medicine, as it provides multimodal analgesia, affecting multiple nociceptive pathways without the use of opioids, in order to minimise opioid-related side effects. This article presents the cases of five dogs undergoing surgical correction of abnormalities associated with brachycephalic obstructive airway syndrome, all of whom received opioid-free anaesthesia for surgery. All dogs received a bilateral maxillary nerve block with bupivacaine 0.5% and a combination of non-opioid analgesic drugs. Buprenorphine was allowed during the postoperative period, based on pain assessment. Three out of five dogs received buprenorphine 6–7 hours after the nerve block was performed. Opioid-free anaesthesia provided adequate conditions for surgery and no adverse effects were reported. Prospective controlled studies comparing opioid-free anaesthesia with opioid-based techniques are required to elucidate whether or not opioid-free anaesthesia confers objective advantages.

Perceptual correlates of homosynaptic long-term potentiation in human nociceptive pathways: a replication study

Animal studies have shown that high-frequency stimulation (HFS) of peripheral C-fibres induces long-term potentiation (LTP) within spinal nociceptive pathways. The aim of this replication study was to assess if a perceptual correlate of LTP can be observed in humans. In 20 healthy volunteers, we applied HFS to the left or right volar forearm. Before and after applying HFS, we delivered single electrical test stimuli through the HFS electrode while a second electrode at the contra-lateral arm served as a control condition. Moreover, to test the efficacy of the HFS protocol, we quantified changes in mechanical pinprick sensitivity before and after HFS of the skin surrounding both electrodes. The perceived intensity was collected for both electrical and mechanical stimuli. After HFS, the perceived pain intensity elicited by the mechanical pinprick stimuli applied on the skin surrounding the HFS-treated site was significantly higher compared to control site (heterotopic effect). Furthermore, we found a higher perceived pain intensity for single electrical stimuli delivered to the HFS-treated site compared to the control site (homotopic effect). Whether the homotopic effect reflects a perceptual correlate of homosynaptic LTP remains to be elucidated.