Articles: hyperalgesia.
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The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. ⋯ Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.
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Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We used the foot as a control site and abdomen as the test site. ⋯ The data suggest that participants with CPP are sensitive to both deep tissue and cutaneous inputs, suggesting that central mechanisms may be important in this cohort. We also see phenotypes such as thermal hyperalgesia, which may be the result of peripheral mechanisms, such as irritable nociceptors. This highlights the importance of stratifying patients into clinically meaningful phenotypes, which may have implications for the development of better therapeutic strategies for CPP.
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Curr Pain Headache Rep · Nov 2023
ReviewNeurovascular Compression-Induced Intracranial Allodynia May Be the True Nature of Migraine Headache: an Interpretative Review.
Surgical deactivation of migraine trigger sites by extracranial neurovascular decompression has produced encouraging results and challenged previous understanding of primary headaches. However, there is a lack of in-depth discussions on the pathophysiological basis of migraine surgery. This narrative review provides interpretation of relevant literature from the perspective of compressive neuropathic etiology, pathogenesis, and pathophysiology of migraine. ⋯ Vasodilation, which can be asymptomatic in healthy subjects, may produce compression of cranial nerves in migraineurs at both extracranial and intracranial entrapment-prone sites. This may be predetermined by inherited and acquired anatomical factors and may include double crush-type lesions. Neurovascular compression can lead to sensitization of the trigeminal pathways and resultant cephalic hypersensitivity. While descending (central) trigeminal activation is possible, symptomatic intracranial sensitization can probably only occur in subjects who develop neurovascular entrapment of cranial nerves, which can explain why migraine does not invariably afflict everyone. Nerve compression-induced focal neuroinflammation and sensitization of any cranial nerve may neurogenically spread to other cranial nerves, which can explain the clinical complexity of migraine. Trigger dose-dependent alternating intensity of sensitization and its synchrony with cyclic central neural activities, including asymmetric nasal vasomotor oscillations, may explain the laterality and phasic nature of migraine pain. Intracranial allodynia, i.e., pain sensation upon non-painful stimulation, may better explain migraine pain than merely nociceptive mechanisms, because migraine cannot be associated with considerable intracranial structural changes and consequent painful stimuli. Understanding migraine as an intracranial allodynia could stimulate research aimed at elucidating the possible neuropathic compressive etiology of migraine and other primary headaches.
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Chronic opioid therapy may lead to high level tolerance development, hyperalgesia, and central sensitization, which further complicates long-term therapeutic management of chronic pain patients. In this case, we encounter a patient who was receiving over 15,000 morphine milligram equivalents through their intrathecal pain pump. Unfortunately, the intrathecal pump was inadvertently cut during a spinal surgery. It was deemed unsafe to delivery IV equivalent opioid therapy in this case; instead, the patient was admitted to the ICU and given a four-day ketamine infusion. ⋯ Ketamine may play an important role in attenuating not only tolerance but also acute withdrawal in a setting where rapid or instant weaning from high dose chronic opioid therapy is needed.