The Role of Ion Channels, Receptors, and Neurotransmitters in Modulating Pain Responses after Neural Injury: Implications for Novel Therapeutic Approaches
Vikram Sharma
Department of Pharmacy, Guru Nanak Dev University, Grand Trunk Road, Amritsar, Punjab, 143005, India.
Harish Kumar
Department of Neurobiology, Sri Venkateswara University, Alipiri Road, Tirupati, Andhra Pradesh, 517502, India.
Abstract
Pain arising from neural injury is often characterized by abnormal activity in sensory neurons, leading to persistent pain, hyperalgesia, and allodynia. Central to the modulation of pain responses are ion channels, receptors, and neurotransmitters that regulate neuronal excitability and synaptic transmission. Ion channels such as voltage-gated sodium channels (e.g., Nav1.7, Nav1.8), potassium channels (e.g., Kv7), calcium channels (e.g., Cav2.2), and transient receptor potential (TRP) channels (e.g., TRPV1, TRPA1) play pivotal roles in shaping the excitability of sensory neurons and are often dysregulated following nerve injury. Receptors, including N-methyl-D-aspartate (NMDA) receptors, GABA receptors, and metabotropic glutamate receptors (mGluRs), influence synaptic plasticity and the balance between excitation and inhibition within pain pathways. Neurotransmitters such as glutamate, GABA, substance P, and serotonin modulate the activity of pain circuits in both the peripheral and central nervous systems. Understanding the roles of these molecular components in pain modulation provides a foundation for developing targeted therapeutic approaches. Emerging treatments include selective ion channel blockers, receptor modulators, and agents that enhance inhibitory neurotransmission. This review explores the mechanisms through which ion channels, receptors, and neurotransmitters modulate pain responses after neural injury, emphasizing their potential as targets for novel pain therapies. By targeting these molecular pathways, it may be possible to alleviate chronic pain and improve the quality of life for individuals suffering from pain conditions associated with neural injury.
