Maladaptive motor cortical excitability and connectivity in polyneuropathy with neuropathic pain

Abstract

Background and purpose: Sensory symptoms, especially neuropathic pain, are common in polyneuropathy. Conventional diagnostic tools can evaluate structural or functional impairment of nerves but cannot reveal mechanisms of neuropathic pain. Changes in the brain after polyneuropathy may play roles in the genesis of neuropathic pain. Methods:This cross-sectional study investigated changes of cortical excitability within left primary motor cortex (M1) by measuring resting motor thresholds, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), and afferent inhibition between polyneuropathy patients and controls, and investigated the correlates of these parameters with neuropathic pain and M1 structural and functional connectivity assessed by diffusion tractography imaging and functional magnetic resonance imaging.Results: Thirty-three painful and 15 nonpainful neuropathic patients and 21 controls were enrolled. There were no differences in intraepidermal nerve fiber density, nerve conduction studies, thermal thresholds, or autonomic functional tests between patients with and without neuropathic pain. Compared to controls, neuropathic patients exhibited similar resting motor thresholds or afferent inhibition, but attenuated SICI and augmented ICF, especially in painful patients. Changes of intracortical excitability in neuropathic patients were correlated with intensities of neuropathic pain, and different presentations of SICI and ICF were noted between patients with and without thermal paresthesia. Additionally, short-latency afferent inhibition at an interstimulus interval of 20 ms was associated with structural connectivity of left M1 with brain areas associated with pain perception.Conclusions: Maladaptive cortical excitability with altered structural connectivity in left M1 developed after peripheral nerve degeneration and was associated with neuropathic pain and sensory symptoms in polyneuropathy.

Corticomotor excitability is altered in central neuropathic pain compared with non-neuropathic pain or pain-free patients

“…However, CE was assessed only in the affected hemisphere, and high RMTs were interpreted as related to motor impairment since 68% of CPSP had mild to moderate weakness [20]. We also found significantly defective SICI in patients with neuropathic pain compared to those without chronic pain, as previously reported in samples of neuropathic pain of mixed central and peripheral etiologies [26,44], suggesting motor cortex disinhibition with impaired GABAergic neurotransmission [10,26,48]. Defective intracortical inhibition was also reported in other chronic pain syndromes [35] and acute pain [40].…”

“…Previous studies on non-neuropathic or mixed neuropathic pain patients reported correlations between CE and clinical manifestations of neuropathic pain, including pain intensity [10,26], thermal paresthesia [10], and allodynia [28,44]. Additionally, repetitive TMS was associated with improvement in thermal sensory perception [19,27].…”

“…Indeed, altered motor CE has been observed in different pain syndromes, such as neuropathic pain of peripheral origin, fibromyalgia, and primary headaches [35]. The most commonly described findings in patients with chronic pain suggest motor cortex disinhibition with impaired GABAergic neurotransmission, which has been reported in both hemispheres [10,26,35]. The motor cortex is also the main target for invasive and non-invasive neuromodulation strategies for pain treatment.…”

Dor neuropática central: caracterização clínica, psicofísica e neurofisiológica

“…We also found significantly defective SICI in patients with neuropathic pain compared to those without chronic pain, as previously reported in samples of neuropathic pain of central and peripheral etiologies (86,88). Studies assessing samples composed of patients with peripheral and central neuropathic pain have shown a reduction of intracortical inhibition, suggesting motor cortex disinhibition with impaired GABAergic neurotransmission (86,113,197). Defective intracortical inhibition was also reported in other chronic pain syndromes (52) and acute pain (112).…”

“…Indeed, altered motor CE has been observed in different pain syndromes, such as neuropathic pain of peripheral origin, fibromyalgia, and primary headaches (52). The most commonly described findings suggest motor cortex disinhibition with impaired GABAergic neurotransmission, and these changes were found in both hemispheres (52,86,113). The motor cortex is also the main target for invasive and non-invasive neuromodulation strategies for pain treatment, and it appears to be superior to deep brain stimulation of the thalamus and midbrain (102).…”