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Difference between revisions of "Neuronal Basis of Neuropathic Pain and Neuroprotective Mechanisms of Antiepileptic Drugs"
Neuronal Basis of Neuropathic Pain and Neuroprotective Mechanisms of Antiepileptic Drugs (view source)
Revision as of 11:40, 19 October 2024
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(Created page with "{{Main menu}} {{ArtBy|||autore=Domenico Tropepe|autore2=Diego Centonze|autore3=Paolo Calabrese}} The use of antiepileptic drugs in conditions other than epilepsy has a relatively long history. As early as the mid-1960s, researchers like Campbell conducted the first clinical trials on the use of carbamazepine in the treatment of trigeminal neuralgia. The undesirable effects of first-generation antiepileptic drugs often limited their use. Today, efforts are being made...") |
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Calcium (Ca++) channels are also involved in the generation of allodynia and hyperalgesia following peripheral nerve injury. Subcutaneous administration of an antagonist for N-type but not P- or Q-type channels has attenuated hyperalgesia in partial sciatic nerve ligation (PNL) models, suggesting a local effect of these channels in the genesis of hyperalgesia<ref>Matthews, EA., & Dickenson, AH. (2001). "Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy." *Pain*, 92(1-2), 235-246.</ref>. | Calcium (Ca++) channels are also involved in the generation of allodynia and hyperalgesia following peripheral nerve injury. Subcutaneous administration of an antagonist for N-type but not P- or Q-type channels has attenuated hyperalgesia in partial sciatic nerve ligation (PNL) models, suggesting a local effect of these channels in the genesis of hyperalgesia<ref>Matthews, EA., & Dickenson, AH. (2001). "Effects of spinally delivered N- and P-type voltage-dependent calcium channel antagonists on dorsal horn neuronal responses in a rat model of neuropathy." *Pain*, 92(1-2), 235-246.</ref>. | ||
N-type currents in the dorsal root ganglia of the spinal cord appear to decrease after axotomy. Cannabinoids, via the CB1 receptor, reduce the flow through N-type channels and, in fact, attenuate thermal and mechanical hyperalgesia as well as cold allodynia in the SNL (spinal nerve ligation) model. Gabapentin binds to the !2" subunits of calcium (Ca++) channels and reduces allodynia and hyperalgesia in both animals and humans<ref>Hunter, JC., et al. (1997). "Gabapentin inhibits Ca(2+) influx and glutamate release in the neocortex of rats." *Epilepsy Research*, 27(3), 187-194.</ref><ref>Fink, K., et al. (2000). "Differential effects of gabapentin on neuronal Ca(2+) channel subtypes." *European Journal of Pharmacology*, 400(1), 25-32.</ref>. In summary, after peripheral nerve injury, the following occurs: de novo synthesis of rapidly inactivated channels, downregulation of TTX-resistant Na+ channels, and loss of HVA-type N Ca++ channels. This results not only in the onset of spontaneous pain but also in so-called "central sensitization." | |||
Regarding central mechanisms of neuropathic pain, anatomical reorganization of the spinal cord has been observed, a form of pathological neuroplasticity. In general, it is stated that myelinated Aβ fibers and unmyelinated C fibers of small nociceptive cells terminate in the superficial layers (laminae I and II) of the dorsal horns, while large neurons with myelinated Aα fibers terminate in laminae III and IV. Lamina V is a convergence zone for various nerve afferents. After peripheral injury, synaptic rearrangement occurs, where Aβ fibers arborize into more superficial laminae; as a consequence, second-order neurons, accustomed to high-threshold afferents, receive stimuli from low-threshold mechanoreceptors. Low-threshold sensory information could be interpreted as nociceptive, providing another explanation for allodynia following peripheral injury. It is important to note that effective arborization does not occur until two weeks after the injury, so this mechanism cannot be solely responsible for the onset of allodynia observed in animal models. | Regarding central mechanisms of neuropathic pain, anatomical reorganization of the spinal cord has been observed, a form of pathological neuroplasticity. In general, it is stated that myelinated Aβ fibers and unmyelinated C fibers of small nociceptive cells terminate in the superficial layers (laminae I and II) of the dorsal horns, while large neurons with myelinated Aα fibers terminate in laminae III and IV. Lamina V is a convergence zone for various nerve afferents. After peripheral injury, synaptic rearrangement occurs, where Aβ fibers arborize into more superficial laminae; as a consequence, second-order neurons, accustomed to high-threshold afferents, receive stimuli from low-threshold mechanoreceptors. Low-threshold sensory information could be interpreted as nociceptive, providing another explanation for allodynia following peripheral injury. It is important to note that effective arborization does not occur until two weeks after the injury, so this mechanism cannot be solely responsible for the onset of allodynia observed in animal models. | ||