Adenosine

adenosine

neurotransmitter derived from ATP that serves as a fatigue signal and acts as a biochemical trace of energy use that is produced inside and outside the neuron and is released through transporters rather than vesicles

A1

adenosine receptor main subtype that is in the cerebral cortex, hippocampus, and cerebellum that mediates fatigue

A2A

adenosine receptor main subtype that is involved in the striatum (motivation) and olfactory bulb that mediates fatigue

nucleus accumbens

brain region that has dopamine D2 receptors that promote effortful behavior that can be negative allosterically modulated by A2A adenosine receptors, blocking dopamines stimulating effects

A2B

adenosine receptors that are a lower affinity version of A2A but may be a relevant disease target

A3

adenosine receptors that are found in low levels in the brain but instead play a role in pain processing in the spinal cord such as morphine tolerance and also reduces the excitability and glutamate release of dorsal root ganglion neurons that send pain signals to the brain

inflammatory pain

pain caused by the release of inflammatory mediators

neuropathic pain

pain caused by an increased excitability of nociceptive signalling carrying neurons

ibuprofen

medication that inhibits cyclooxygenase enzymes which in turn blocks the production of prostaglandins

prostaglandins

hormone like compounds that reduce action potenital threshold of TTX resistant sodium channels on pain carrying neurons

central sensitization

process in neuropathic pain where afferant nocicpetine signals have overactive NMDA receptors, reduction in GABA, essentially causing overexcitability