Peripheral nerve and spinal cord injuries, along with other painful syndromes such as fibromyalgia, diabetic neuropathy, chemotherapeutic neuropathy, trigeminal neuralgia, complex regional pain syndrome, and/or irritable bowel syndrome, cause several neuroplasticity changes in the nervous system along its entire axis affecting the different neuronal nuclei. This paper reviews these changes, focusing on the supraspinal structures that are involved in the modulation and processing of pain, including the periaqueductal gray matter, red nucleus, locus coeruleus, rostral ventromedial medulla, thalamus, hypothalamus, basal ganglia, cerebellum, habenula, primary and secondary somatosensory cortex, motor cortex, mammillary bodies, hippocampus, septum, amygdala, cingulated and prefrontal cortex. Hyperexcitability caused by the modification of postsynaptic receptor expression, central sensitization and potentiation of presynaptic delivery of neurotransmitters, as well as the reduction of inhibitory inputs, changes in dendritic spine, neural circuit remodeling, alteration of gray matter, and upregulation of pro-inflammatory mediators (e.g. cytokines) by reactivation of astrocytes and microglial cells are the main functional, structural and molecular neuroplasticity changes observed in the above supraspinal structures, associated with pathological pain. Studying these changes in greater depth may lead to the implementation and improvement of new therapeutic strategies against pathological pain