Central and peripheral mechanisms of pain modulationthe role of the Locus coeruleus and pupillary dynamics in neuropathic and inflammatory pain
type: CreativeWork
description: Pain is a complex sensory and emotional experience that results from the interaction between peripheral nociceptive input and central processing in the nervous system. Despite its clinical relevance and social impact, the management of pain, particularly chronic pain remains a significant challenge. Current treatments often provide insufficient relief, and only a limited number of findings from basic research have successfully translated into effective therapies. This translational gap underscores the need for improved preclinical models and for objective physiological biomarkers that can reliably reflect nociceptive processing and treatment efficacy. An additional and often underestimated factor in pain research is biological sex, which strongly influences pain perception, prevalence, and treatment outcomes. Epidemiological studies consistently show that women are more frequently affected by chronic and inflammatory pain disorders than men. The underlying mechanisms are multifactorial, involving hormonal modulation, immune responses, and central nervous system differences. Among these, the locus coeruleus (LC), the main noradrenergic nucleus in the brainstem, exhibits pronounced sexual dimorphism in both its structure and function. The LC is a key node in the modulation of pain, arousal, and stress, and its projections reach widespread regions of the brain and spinal cord (SC). Differences in LC organization, neuronal density, and hormonal sensitivity between males and females may contribute to sex-dependent variations in pain modulation and autonomic regulation. The main objective of this doctoral thesis was to investigate the central and peripheral neurophysiological mechanisms underlying pain modulation in models of nerve injury and inflammation. This was achieved by assessing the contribution of the LC as a central node and pupillary dynamics as a peripheral readout, with the ultimate goal of establishing pupillary responses as a translational biomarker for the…
abstract: Pain is a complex sensory and emotional experience that results from the interaction between peripheral nociceptive input and central processing in the nervous system. Despite its clinical relevance and social impact, the management of pain, particularly chronic pain remains a significant challenge. Current treatments often provide insufficient relief, and only a limited number of findings from basic research have successfully translated into effective therapies. This translational gap underscores the need for improved preclinical models and for objective physiological biomarkers that can reliably reflect nociceptive processing and treatment efficacy. An additional and often underestimated factor in pain research is biological sex, which strongly influences pain perception, prevalence, and treatment outcomes. Epidemiological studies consistently show that women are more frequently affected by chronic and inflammatory pain disorders than men. The underlying mechanisms are multifactorial, involving hormonal modulation, immune responses, and central nervous system differences. Among these, the locus coeruleus (LC), the main noradrenergic nucleus in the brainstem, exhibits pronounced sexual dimorphism in both its structure and function. The LC is a key node in the modulation of pain, arousal, and stress, and its projections reach widespread regions of the brain and spinal cord (SC). Differences in LC organization, neuronal density, and hormonal sensitivity between males and females may contribute to sex-dependent variations in pain modulation and autonomic regulation. The main objective of this doctoral thesis was to investigate the central and peripheral neurophysiological mechanisms underlying pain modulation in models of nerve injury and inflammation. This was achieved by assessing the contribution of the LC as a central node and pupillary dynamics as a peripheral readout, with the ultimate goal of establishing pupillary responses as a translational biomarker for the…
author: López Martín, Carolina
language: eng
license: http://creativecommons.org/licenses/by-nc-nd/4.0/
date published: 2026
date modified: 2026-07-24T01:29:24Z
provider: Universidad de Cadiz
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Universidad de Cadiz

PropertyValue
property ID: Handle
value: http://hdl.handle.net/10498/39657