Adaptive and Maladaptive Neural Plasticity in Pain Processing: Insights into Mechanisms of Neural Injury and Strategies for Targeted Interventions

Abstract

Pain processing is inherently dynamic, involving changes in the nervous system that can be either adaptive or maladaptive. Adaptive neural plasticity is essential for recovery from injury, facilitating adjustments in sensory pathways and promoting healing. In contrast, maladaptive plasticity contributes to the persistence of pain by altering synaptic function, neuronal excitability, and network connectivity, leading to chronic pain conditions. Following nerve injury, plastic changes occur at multiple levels of the nervous system, including the peripheral nervous system (PNS), spinal cord, and brain, resulting in heightened pain sensitivity and abnormal pain responses. Key molecular mechanisms underlying these changes include alterations in ion channels, receptor function, and intracellular signaling pathways such as mitogen-activated protein kinases (MAPKs) and neurotrophic factors like BDNF (brain-derived neurotrophic factor). Maladaptive plasticity leads to phenomena such as central sensitization, where spinal neurons exhibit increased responsiveness to sensory inputs, and altered cortical representations of pain. Understanding the balance between adaptive and maladaptive plasticity provides insights into potential therapeutic strategies aimed at promoting beneficial neural adaptations while suppressing pathological changes. This review explores the mechanisms of neural plasticity in pain processing, highlighting molecular and cellular processes involved in neural injury and repair. We discuss targeted interventions, including pharmacological agents, neuromodulation, and regenerative approaches, that aim to modulate neural plasticity and improve outcomes for individuals suffering from chronic pain.