CASE REPORT | doi:10.20944/preprints202208.0165.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: neuralgia; earache; facial pain; neuropathic pain; geniculate neuralgia; nervus intermedius; otalgia; gabapentin
Online: 9 August 2022 (03:20:29 CEST)
(1) Background: Painful nervus intermedius neuropathy (e.g., geniculate neuralgia) involves continuous or near-continuous pain affecting the distribution of the intermedius nerve(s). The diagnosis of this entity is challenging, particularly when the clinical and demographic features do not resemble the typical presentation of this condition. To the best of our knowledge, only three case reports have described the occurrence of nervus intermedius neuropathy in young patients. (2) Case Description: A 13-year-old female referred to the Orofacial Pain clinic with a complaint of pain located deep in the right ear and mastoid area. The pain was described as a constant throbbing and dull, with an intensity of 7/10 on numerical rating scale, characterized by superimposed brief paroxysms of severe sharp pain. The past treatments included ineffective pharmacological and irreversible surgical approaches. After a comprehensive evaluation, a diagnosis of idiopathic painful nervus intermedius neuropathy was given, which was successfully managed with the use of gabapentin. (3) Conclusions and Practical Implications: The diagnosis and treatment of neuropathic pain affecting the nervus intermedius can be challenging due to the complex nature of the sensory innervation of the ear. The diagnosis can be even more challenging in cases of atypical clinical and demographic presentations, which in turn may result in unsuccessful, unnecessary, and irreversible treatments. Multidisciplinary teams and constant knowledge update are fundamental to provide good quality of care to our patients and to not overlook any relevant signs or symptoms.
HYPOTHESIS | doi:10.20944/preprints202002.0127.v1
Subject: Keywords: Voltage-gated calcium channel (VGCC); α2δ-1 subunit; Gabapentin (GBP); Local conformational inflexibility; VGCC trafficking
Online: 10 February 2020 (11:59:38 CET)
For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.