Neurophatic pain
- Autores: Alejandro Barroso González
- Directores de la Tesis: Inmaculada Bellido Estévez (dir. tes.), Manuel Rodríguez López (dir. tes.), Michael Andrew Thacker (dir. tes.)
- Lectura: En la Universidad de Málaga ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: Aurelio Gómez Luque (presid.), Rosalía de la Torre Liébanas (secret.), Christoforos Tsantoulas (voc.)
- Materias:
- Enlaces
- Tesis en acceso abierto en: RIUMA
- Resumen
Neuropathic pain (NP) embraces a broad range of conditions linked with a disease or lesion of the peripheral or central somatosensory system and its prevalence in the general population may be as high as 7-10%. Up to the present, the larger part of our understanding of pain mechanisms come from basic sciences studies which has resulted in a vast increase in our knowledge. The obvious issues in translational pain research reveal the limitations of certain experimental models, and on that account result of limitations in clinical research. In spite of such difficulties, the scientific community wish for a better understanding of pain mechanisms helped by the new insights of basic research. For that reason, the first of the three parts of this work aim to recognise additional changes in the somatosensory system through a series of experiments done in an experimental model of NP.
NP following peripheral nerve injury is associated with hyperexcitability in damaged myelinated sensory axons, which begins to normalise over time. We investigated the composition and distribution of shaker-type-potassium channels (Kv1 channels) within the nodal complex of myelinated axons following injury. At the neuroma that forms after damage, expression of Kv1.1 and 1.2 was markedly decreased. In contrast Kv1.4 and 1.6, which were hardly detectable in the naıve state, showed increased expression following injury. Within the dorsal root we noted a redistribution of Kv1-channels towards the paranode. Blockade of Kv1 channels with a-DTX after injury reinstated hyperexcitability of A-fibre axons and enhanced mechanosensitivity. Changes in the molecular composition and distribution of axonal Kv1 channels, therefore represents a protective mechanism to suppress the hyperexcitability of myelinated sensory axons that follows nerve injury.
To date, both basic and human data suggest that a lesion of afferent pathways is required for development of NP. In addition, numerous studies demonstrate that not one but various mechanisms can induce to NP. This not only evidence the complexity of NP, but also underline the clinical significance of identifying underlying pain mechanisms in every single patient. Because different management plans are required for different pain mechanisms, a mechanism-based treatment approach can guide clinicians to better outcomes. With these concepts in mind the second chapter of this study aim to clarify some links between one of the most novel techniques used in the diagnosis of NP, the Quantitative Sensory Testing (QST), which has been used to determine the pathological mechanisms functioning and the phenotype expressed. With the painDETECT Questionnaire as screening tool for NP, we analyse whether the overall PDQ score or its items reflect phenotypes of sensory loss in NP as determined by QST. The results of our study conclude that patients with loss of thermal sensation significantly more often reported pain evoked by light touch, and patients with loss of mechanical sensation significantly more often reported numbness and significantly less often burning sensations and pain evoked by light touch. Although the PDQ was not designed to assess sensory loss, single items reflect thermal and/or mechanical sensory loss at group level, but because of substantial variability, the PDQ does not allow for individual allocation of patients into sensory profiles.
Finally, the last part of this thesis focuses its attention in the management of NP, more precisely in Complex Regional Pain Syndrome (CRPS) in children. This chapter review the evidence for invasive pain procedures along with presenting a management algorithm for paediatric CRPS, including invasive procedures for patients who do not respond to the conventional first-line treatment. We also report on the course and management of a series of children diagnosed with CRPS, applying the multidisciplinary management approach described above. We conclude that because of the severity and rapid progression of the symptoms in CRPS an early diagnosis of the condition together with comprehensive, and individualized multidisciplinary treatment offers children with CRPS the best opportunity for a complete recovery. Within this approach we encourage clinicians to consider invasive procedures as a reliable option of treatment.
