Additionally, CTTH patients exhibit decreased thermal and pain thresholds which further bolsters support for central sensitization occurring in CTTH.The alterations in physiology that lead to overall process of central sensitization involve changes at the level of neural tracts, neurotransmitters and their receptors, the neural synapse, and the post-synaptic membrane. Evidence suggests dysfunction in supraspinal descending inhibitory pain pathways may contribute to the pathogenesis of central sensitization in CTTH. Neurotransmitters
Specific neuronal receptors and neurotransmitters thought to be most involved include NMDA and AMPA receptors, glutamate, serotonin (5-HT), β-endorphin, and nitric oxide (NO). Of the neurotransmitters, NO plays a major role in central pain pathways and likely contributes to the process of central sensitization. Briefly, the enzyme nitric oxide synthase (NOS) forms NO which ultimately results in vasodilatation and activation of central nervous system pain pathways. Serotonin may also be of significant importance and involved in malfunctioning pain filter located in the brain stem. The view is that the brain misinterprets information—for example from the temporal muscle or other muscles—and interprets this signal as pain. Evidence for this theory comes from the fact that chronic tension-type headaches may be successfully treated with certain antidepressants such as nortriptyline. However, the analgesic effect of nortriptyline, as well as amitriptyline in chronic tension-type headache, is not solely due to serotonin reuptake inhibition, and likely other mechanisms are involved. Synapses
Regarding synaptic level changes, homosynaptic facilitation and heterosynaptic facilitation are both likely to be involved in central sensitization.
The Food and Drug Administration has granted a fast track designation to sotorasib for the treatment of metastatic non-small-cell lung carcinoma with the G12C KRAS mutation. Chemistry and pharmacology
Sotorasib can exist in either of two atropisomeric forms and one is more active than the other. It selectively forms an irreversible covalent bond to the sulfur atom in the cysteine residue that is present in the mutated form of KRAS, but not in the normal form. History
Researchers evaluated the efficacy of sotorasib in a study of 124 participants with locally advanced or metastatic KRAS G12C-mutated non-small cell lung cancer with disease progression after receiving an immune checkpoint inhibitor and/or platinum-based chemotherapy. The major outcomes measured were objective response rate (proportion of participants whose tumor is destroyed or reduced) and duration of response. The objective response rate was 36% and 58% of those participants had a duration of response of six months or longer.The U.S. Food and Drug Administration (FDA) granted the application for sotorasib orphan drug, fast track, priority review, and breakthrough therapy designations. The FDA collaborated with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada and the United Kingdom Medicines and Healthcare products Regulatory Agency (MHRA). The application reviews are ongoing at the other regulatory agencies.The FDA granted approval of Lumakras to Amgen Inc.

Society and culture
Economics
At introduction, in the United States, Sotorasib costs US$17,900 per month.