Pain perception and migraine

Background: It is well-known that both inter-and intra-individual differences exist in the perception of pain; this is especially true in migraine, an elusive pain disorder of the head. Although electrophysiology and neuroimaging techniques have greatly contributed to a better understanding of the mechanisms involved in migraine during recent decades, the exact characteristics of pain threshold and pain intensity perception remain to be determined, and continue to be a matter of debate.Objective: The aim of this review is to provide a comprehensive overview of clinical, electrophysiological, and functional neuroimaging studies investigating changes during various phases of the so-called "migraine cycle" and in different migraine phenotypes, using pain threshold and pain intensity perception assessments.Methods: A systematic search for qualitative studies was conducted using search terms "migraine," "pain," "headache," "temporal summation," "quantitative sensory testing," and "threshold," alone and in combination (subject headings and keywords). The literature search was updated using the additional keywords "pain intensity," and "neuroimaging"to identify full-text papers written in English and published in peer-reviewed journals, using PubMed and Google Scholar databases. In addition, we manually searched the reference lists of all research articles and review articles.Conclusion: Consistent data indicate that pain threshold is lower during the ictal phase than during the interictal phase of migraine or healthy controls in response to pressure, cold and heat stimuli. There is evidence for preictal sub-allodynia, whereas interictal results are conflicting due to either reduced or no observed difference in pain threshold. On the other hand, despite methodological limitations, converging observations support the concept that migraine attacks may be characterized by an increased pain intensity perception, which normalizes between episodes. Nevertheless, future studies are required to longitudinally evaluate a large group of patients before and after pharmacological and non-pharmacological interventions to investigate phases of the migraine cycle, clinical parameters of disease severity and chronic medication usage

Neural plasticity in common forms of chronic headaches

Headaches are universal experiences and among the most common disorders. While headache may be physiological in the acute setting, it can become a pathological and persistent condition.The mechanisms underlying the transition from episodic to chronic pain have been the subject of intense study. Using physiological and imaging methods, researchers have identified a number of different forms of neural plasticity associated with migraine and other headaches, including peripheral and central sensitization, and alterations in the endogenous mechanisms of pain modulation. While these changes have been proposed to contribute to headache and pain chronification, some findings are likely the results of repetitive noxious stimulation, such as atrophy of brain areas involved in pain perception and modulation. In this review, we provide a narrative overview of recent advances on the neuroimaging, electrophysiological and genetic aspects of neural plasticity associated with the most common forms of chronic headaches, including migraine, cluster headache, tension-type headache, and medication overuse headache

Neurostimulation Techniques for the Modulation of Pain

Non-invasive brain stimulation (NIBS) is increasingly proposed as a therapeutic intervention for many neurological and psychiatric disorders, including pain, depression, obsessive compulsive disorder, and anxiety. While neuromodulation as an intervention for pain relief has a well-established scientific basis, evidence is largely restricted to invasive stimulation that targets the spinal cord. Novel non-invasive methodologies instead predominately target cortical processing of pain and thus raise interesting questions about how the most effective pain relief can be achieved. Functional magnetic resonance imaging (fMRI) studies show a widespread and distributed activation of brain areas during pain. This diverse activity is often referred to as the “pain neuromatrix” and can lead to the proposal for different possible target areas for pain relief. Neuromodulation could target brain regions of pain processing areas responsible for sensorimotor processing or alternatively regions responsible for the affective and evaluative aspects of the subjective pain experience. The chapter addresses the different approaches currently taken in the use of non-invasive neuromodulation for altering pain both in an experimental setting and the challenges involved in the translation of these techniques to a diverse range of chronic pain conditions

Brain Circuits Involved in the Development of Chronic Musculoskeletal Pain: Evidence From Non-invasive Brain Stimulation

It has been well-documented that the brain changes in states of chronic pain. Less is known about changes in the brain that predict the transition from acute to chronic pain. Evidence from neuroimaging studies suggests a shift from brain regions involved in nociceptive processing to corticostriatal brain regions that are instrumental in the processing of reward and emotional learning in the transition to the chronic state. In addition, dysfunction in descending pain modulatory circuits encompassing the periaqueductal gray and the rostral anterior cingulate cortex may also be a key risk factor for pain chronicity. Although longitudinal imaging studies have revealed potential predictors of pain chronicity, their causal role has not yet been determined. Here we review evidence from studies that involve non-invasive brain stimulation to elucidate to what extent they may help to elucidate the brain circuits involved in pain chronicity. Especially, we focus on studies using non-invasive brain stimulation techniques [e.g., transcranial magnetic stimulation (TMS), particularly its repetitive form (rTMS), transcranial alternating current stimulation (tACS), and transcranial direct current stimulation (tDCS)] in the context of musculoskeletal pain chronicity. We focus on the role of the motor cortex because of its known contribution to sensory components of pain via thalamic inhibition, and the role of the dorsolateral prefrontal cortex because of its role on cognitive and affective processing of pain. We will also discuss findings from studies using experimentally induced prolonged pain and studies implicating the DLPFC, which may shed light on the earliest transition phase to chronicity. We propose that combined brain stimulation and imaging studies might further advance mechanistic models of the chronicity process and involved brain circuits. Implications and challenges for translating the research on mechanistic models of the development of chronic pain to clinical practice will also be addressed

The phantom limb

Thesis (M.D.)—Boston Universit

Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action.

Well-established in the field of bioelectronic medicine, Spinal Cord Stimulation (SCS) offers an implantable, non-pharmacologic treatment for patients with intractable chronic pain conditions. Chronic pain is a widely heterogenous syndrome with regard to both pathophysiology and the resultant phenotype. Despite advances in our understanding of SCS-mediated antinociception, there still exists limited evidence clarifying the pathways recruited when patterned electric pulses are applied to the epidural space. The rapid clinical implementation of novel SCS methods including burst, high frequency and dorsal root ganglion SCS has provided the clinician with multiple options to treat refractory chronic pain. While compelling evidence for safety and efficacy exists in support of these novel paradigms, our understanding of their mechanisms of action (MOA) dramatically lags behind clinical data. In this review, we reconstruct the available basic science and clinical literature that offers support for mechanisms of both paresthesia spinal cord stimulation (P-SCS) and paresthesia-free spinal cord stimulation (PF-SCS). While P-SCS has been heavily examined since its inception, PF-SCS paradigms have recently been clinically approved with the support of limited preclinical research. Thus, wide knowledge gaps exist between their clinical efficacy and MOA. To close this gap, many rich investigative avenues for both P-SCS and PF-SCS are underway, which will further open the door for paradigm optimization, adjunctive therapies and new indications for SCS. As our understanding of these mechanisms evolves, clinicians will be empowered with the possibility of improving patient care using SCS to selectively target specific pathophysiological processes in chronic pain

Thalamo-cortical network activity between migraine attacks. Insights from MRI-based microstructural and functional resting-state network correlation analysis

BACKGROUND: Resting state magnetic resonance imaging allows studying functionally interconnected brain networks. Here we were aimed to verify functional connectivity between brain networks at rest and its relationship with thalamic microstructure in migraine without aura (MO) patients between attacks. METHODS: Eighteen patients with untreated MO underwent 3 T MRI scans and were compared to a group of 19 healthy volunteers (HV). We used MRI to collect resting state data among two selected resting state networks, identified using group independent component (IC) analysis. Fractional anisotropy (FA) and mean diffusivity (MD) values of bilateral thalami were retrieved from a previous diffusion tensor imaging study on the same subjects and correlated with resting state ICs Z-scores. RESULTS: In comparison to HV, in MO we found significant reduced functional connectivity between the default mode network and the visuo-spatial system. Both HV and migraine patients selected ICs Z-scores correlated negatively with FA values of the thalamus bilaterally. CONCLUSIONS: The present results are the first evidence supporting the hypothesis that an abnormal resting within networks connectivity associated with significant differences in baseline thalamic microstructure could contribute to interictal migraine pathophysiology

Developing a Brain‐Based, Non‐Invasive Treatment for Pain

Chronic pain cost society more than $500 billion each year and contributes to the ongoing opioid overdose crisis. Substantial risks and low efficacy are associated with opiate usage for chronic pain. This dissertation seeks to fill the urgent need for a new pain treatment using a neural-circuit based approach in healthy controls and chronic pain patients. First, we performed a single-blind study examining the causal effects of transcranial magnetic stimulation (TMS), compared to a well-matched control condition. Using interleaved TMS/fMRI we explored brain activation in response to dorsolateral prefrontal cortex (DLPFC) stimulation in 20 healthy controls. This study tested the hypothesis that the TMS evoked responses would be in frontostriatal locations. Consistent with this hypothesis active TMS, compared to the control, led to significantly greater activity in the caudate, thalamus and anterior cingulate cortex (ACC). Building on these findings, we developed a single-blind, sham-controlled study examining two TMS strategies for analgesia in 45 healthy controls. We completed an fMRI thermal pain paradigm before and after modulatory repetitive TMS at either the DLPFC or the medial prefrontal cortex (MPFC). Despite a role in pain processing, the MPFC has not yet been explored as a target for analgesia. Only MPFC stimulation significantly improved behavioral pain measures. These effects were associated with increased motor and parietal cortex activity during the pain task. We then supplement these findings by testing the hypothesis that chronic pain patients who use opioids (n=14) would have elevated brain responses to thermal pain relative to healthy controls (n=14). Despite indistinguishable self-report measures, we found increased brain activity in the ACC and sensory areas in patients which were positively correlated with opioid dose. We conclude by evaluating the feasibility of these approaches in chronic pain patients, reporting preliminary findings from a pilot study examining the two treatment strategies tested previously in controls. Collectively, our findings support a circuits-first approach to pain treatment. Though MPFC stimulation was effective in reducing pain in healthy controls, further work is required to confirm these results in a chronic pain population, as chronic pain and opioid usage alter how the brain processes the pain experience