Main pathophysiological mechanisms of NP
| Level of the nervous system | Pathophysiological mechanisms |
|---|---|
| PNS | |
| Peripheral nerve | ▸ Release of pain-related mediators (BK, PG, TNFα, ILs, His, ATP and potassium ions) ▸ Upregulation of TRP proteins in uninjured C fibres ▸ Dysregulation of the synthesis or the functioning of voltage-gated sodium channels ▸ Dysregulation of the synthesis or the functioning of potassium channels |
| Dorsal root ganglion | ▸ Increased activity in dorsal root ganglions ▸ Dorsal root ganglion infiltration by activated macrophages ▸ Increased synthesis of proinflammatory cytokines in dorsal root ganglions |
| CNS | |
| Spinal cord neurones | ▸ Functional reorganisation (neuroplasticity) of dorsal horn nociceptive neurones ▸ Increased release of glutamate and substance P ▸ Increased expression of Nav1.3 in dorsal horn second-order neurones ▸ Increased activity in voltage-gated calcium channels ▸ Selective apoptotic loss of GABA-releasing interneurones ▸ Reduction of KCC2 in lamina I neurone ▸ Intracellular changes induced by the activation of NMDA receptors or other receptors (ie, glutamate metabotropic receptors) by excitatory amino acids released by primary afferents ▸ Microglial activation |
| Brainstem (descending pain-controlling systems) | ▸ Loss of function in descending inhibitory opioidergic, serotoninergic and noradrenergic pathways ▸ Changes in the modulatory control of nociceptive pathways |
| Brain | ▸ Functional reorganisation (neuroplasticity) of thalamic and cortical (prefrontal and somatosensory) nociceptive neurones |
ATP, adenosine-5'-triphosphate; BK, bradykinin; CNS, central nervous system; GABA, γ-aminobutyric acid; His, histamine; IL, interleukin; KCC2, potassium chloride co-transporter 2; Nav1.3, voltage-gated sodium channel 1.3; NMDA, N-methyl-D-aspartate; NP, neuropathic pain; PG, prostaglandin; PNS, peripheral nervous system; TNFα, tumour necrosis factor α; TRP, transient potential receptor.