The journal of headache and pain
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Transforming growth factor-βs (TGF-βs) are a group of multifunctional proteins that have neuroprotective roles in various experimental models. We previously reported that intrathecal (i.t.) injections of TGF-β1 significantly inhibit neuropathy-induced thermal hyperalgesia, spinal microglia and astrocyte activation, as well as upregulation of tumor necrosis factor-α. However, additional cellular mechanisms for the antinociceptive effects of TGF-β1, such as the mitogen-activated protein kinase (MAPK) pathway, have not been elucidated. During persistent pain, activation of MAPKs, especially p38 and extracellular signal-regulated kinase (ERK), have crucial roles in the induction and maintenance of pain hypersensitivity, via both nontranscriptional and transcriptional regulation. In the present study, we used a chronic constriction injury (CCI) rat model to explore the role of spinal p38 and ERK in the analgesic effects of TGF-β1. ⋯ The present results demonstrate that suppressing p38 and ERK activity affects TGF-β1-induced analgesia during neuropathy.
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Neurotrophic factors have been implicated in hyperalgesia and peripheral levels of these molecules are altered in migraine pathophysiology. Artemin, a vasculature-derived neurotrophic factor, contributes to pain modulation and trigeminal primary afferent sensitization through binding its selective receptor GFRα3. The distribution of artemin and GFRα3 in the dura mater raises an anatomy supports that they may be involved in migraine. In this study we evaluated the expression of artemin and GFRα3 in an animal migraine model that may be relevant for migraine. ⋯ The findings suggest that artemin and GFRα3 play an important role in the pathogenesis of migraine and may represent potential therapeutic targets for the treatment of migraine.
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Tension-type headache and other primary headaches may be triggered or aggravated by disorders of pericranial muscles, which is possibly due to convergent or collateral afferent input from meningeal and muscular receptive areas. In rodent models high extracellular concentrations of ATP caused muscle nociception and central sensitization of second order neurons. In a rat model of meningeal nociception we asked if spinal trigeminal activity induced by ATP can be modulated by local anaesthesia of distinct muscles. ⋯ Distinct spinal trigeminal neurons processing meningeal nociceptive information are under the control of convergent afferent input from several pericranial muscles. Blockade of at least one of these inputs can normalize central trigeminal activity. This may explain why therapeutic manipulations of head muscles can be beneficial in primary headaches.