Pain
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Mambalgins are 57-amino acid peptides isolated from snake venom that evoke naloxone-resistant analgesia after local (intraplantar) and central (intrathecal) injections through inhibition of particular subtypes of acid-sensing ion channels (ASICs). We now show that mambalgins also have an opioid-independent effect on both thermal and mechanical inflammatory pain after systemic intravenous (i.v.) administration and are effective against neuropathic pain. ⋯ These data further support the role of peripheral and central ASIC1-containing channels in pain, demonstrate their participation in neuropathic pain, and highlight differences in the repertoire of channels involved in different pain conditions. They also strengthen the therapeutic potential of mambalgin peptides that are active in a broader range of experimental pain models and through i.v. systemic delivery.
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Trigeminal neuropathic pain is a well-recognized complication of the demyelinating disease multiple sclerosis (MS). However, the mechanisms underlying MS-related trigeminal neuropathic pain are poorly understood. This can be attributed, at least in part, to the lack of an animal model that exhibits trigeminal pathology similar to that described in MS. ⋯ We also observe demyelination of the intra- and extra-pontine aspects of the trigeminal sensory root and the spinal trigeminal tract. This is the first study to show orofacial sensory disturbances and trigeminal demyelination in EAE. Collectively, our data suggest that EAE may be a useful model for understanding MS-related trigeminal neuropathic pain conditions such as trigeminal neuralgia.
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The treatment of neuropathic pain by neuromodulation is an objective for more than 40 years in modern clinical practice. With respect to spinal cord and deep brain structures, the cerebral cortex is the most recently evaluated target of invasive neuromodulation therapy for pain. In the early 90s, the first successes of invasive epidural motor cortex stimulation (EMCS) were published. ⋯ It is therefore important to know the principles and to assess the merit of these techniques on the basis of a rigorous assessment of the results, to avoid fad. Various types of chronic neuropathic pain syndromes can be significantly relieved by EMCS or repeated daily sessions of high-frequency (5-20 Hz) rTMS or anodal tDCS over weeks, at least when pain is lateralized and stimulation is applied to the motor cortex contralateral to pain side. However, cortical stimulation therapy remains to be optimized, especially by improving EMCS electrode design, rTMS targeting, or tDCS montage, to reduce the rate of nonresponders, who do not experience clinically relevant effects of these techniques.
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The full role of adult hippocampal neurogenesis (AHN) remains to be determined, yet it is implicated in learning and emotional functions, and is disrupted in negative mood disorders. Recent evidence indicates that AHN is decreased in persistent pain consistent with the idea that chronic pain is a major stressor, associated with negative moods and abnormal memories. Yet, the role of AHN in development of persistent pain has remained unexplored. ⋯ Downregulating neurogenesis reversibly diminished or blocked persistent pain; oppositely, upregulating neurogenesis led to prolonged persistent pain. Moreover, we could dissociate negative mood from persistent pain. These results suggest that AHN-mediated hippocampal learning mechanisms are involved in the emergence of persistent pain.
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Motor vehicle collision (MVC) can trigger chronic widespread pain (CWP) development in vulnerable individuals. Whether such CWP typically develops through the evolution of pain from regional to widespread or through the early development of widespread pain with nonrecovery is currently unknown. We evaluated the trajectory of CWP development (American College of Rheumatology criteria) among 948 European-American individuals who presented to the emergency department (ED) for care in the early aftermath of MVC. ⋯ Linear solution plots supported a nonrecovery model. Although the number of body regions with pain in the non-CWP group steadily declined, the number of body regions with pain in the CWP trajectory group (192/895, 22%) remained relatively constant over time. These data support the hypothesis that individuals who develop CWP after MVC develop widespread pain in the early aftermath of MVC, which does not remit.