Articles: hyperalgesia.
-
Primary hyperalgesia to mechanical and thermal stimuli are major clinical symptoms of inflammatory pain and can be induced experimentally by ultraviolet-B (UV-B) irradiation in humans. We set-up a pig model in order to have more options for pharmacological intervention on primary hyperalgesia. Pig skin was irradiated with a dose one- to threefold higher than the minimum erythema dose (MED) and investigated for mechanical and heat responsiveness 24 and 48 h post UV-B treatment. ⋯ No significant differences of mechanically or thermally induced hypersensitivity were seen between 24 and 48 h after irradiation. We conclude that UV-B induced mechanical and heat sensitization of primary afferent nociceptors can be assessed in pig skin, providing a new human-like model of primary hyperalgesia. Sensitization of primarily mechano-insensitive (silent) nociceptors, which are underlying the flare response in humans, most probably contributes to the observation presented here.
-
To investigate allodynia in patients with different primary headaches. ⋯ Allodynia is not specific to migraine but is frequent in all headache patients: acute allodynia was reported in half those interviewed and in over a third of patients in each headache category; interictal allodynia was reported by nearly 25%.
-
Brain Behav. Immun. · Feb 2008
IL-1 beta signaling is required for mechanical allodynia induced by nerve injury and for the ensuing reduction in spinal cord neuronal GRK2.
Many neurotransmitters involved in pain perception transmit signals via G protein-coupled receptors (GPCRs). GPCR kinase 2 (GRK2) regulates agonist-induced desensitization and signaling of multiple GPCRs and interacts with downstream molecules with consequences for signaling. In general, low GRK2 levels are associated with increased responses to agonist stimulation of GPCRs. ⋯ Moreover, spinal cord GRK2 expression was not decreased in IL-1R(-/-) mice after L5 SNT. These data show that IL-1 beta signaling is not only required for the development of mechanical allodynia, but also to reduce neuronal GRK2 expression. These results suggest a functional relation between the L5 SNT-induced IL-1 beta-mediated decrease in GRK2 and development of mechanical allodynia.
-
Guanethidine displaces noradrenaline from sympathetic varicosities, and blocks sympathetic noradrenergic neurotransmission by inhibiting the release of noradrenaline from depleted neural stores. The aim of this study was to determine whether depletion of noradrenaline with guanethidine would oppose thermal hyperalgesia and/or electrically-evoked pain in mildly-burnt skin. Guanethidine was transferred by iontophoresis into a small patch of skin on the forearm of 35 healthy human subjects. ⋯ These findings indicate that ongoing sympathetic neural discharge does not normally influence thermal hyperalgesia in inflamed skin, because depleting noradrenergic stores had no effect. However, electrically-evoked release of noradrenaline may increase nociceptive sensations. Further clarification of this human pain model could provide insights into the mechanism of adrenergic hyperalgesia in certain neuropathic pain syndromes.
-
Peripheral nerve injury may lead to the formation of a painful neuroma. In patients, palpating the tissue overlying a neuroma evokes paraesthesias/dysaesthesias in the distribution of the injured nerve. Previous animal models of neuropathic pain have focused on the mechanical hyperalgesia and allodynia that develops at a location distant from the site of injury and not on the pain from direct stimulation of the neuroma. ⋯ The neuroma tenderness (but not the hyperalgesia) was reversed by local lidocaine injection and by proximal transection of the tibial nerve. Afferents originating from the neuroma exhibited spontaneous activity and responses to mechanical stimulation of the neuroma. The TNT model provides a useful tool to investigate the differential mechanisms underlying the neuroma tenderness and mechanical hyperalgesia associated with neuropathic pain.