The brain creates the sensation of pain to direct attention to the body part, so the threat can be mitigated; this process is called nociception.

This barrier or threshold contrasts with the more sensitive visual, auditory, olfactory, taste, and somatosensory responses to stimuli.

Simple activation of a nociceptor does not always lead to perceived pain, because the latter also depends on the frequency of the action potentials, integration of pre- and postsynaptic signals, and influences from higher or central processes.

In earlier centuries, scientists believed that animals were like mechanical devices that transformed the energy of sensory stimuli into motor responses.

The process is difficult due to invasive methods that could change the cellular activity of nociceptors being studied, the inability to record from small neuronal structures, and uncertainties in animal model systems as to whether a response should be attributed to pain or some other factor.

[4] The peripheral terminal of the mature nociceptor is where the noxious stimuli are detected and transduced into electrical energy.

[7] When the electrical energy reaches a threshold value, an action potential is induced and driven towards the central nervous system (CNS).

Massive or prolonged input to a C fiber results in a progressive build up in the dorsal horn of the spinal cord; this phenomenon called wind-up is similar to tetanus in muscles.

An interesting finding related to cold stimuli is that tactile sensibility and motor function deteriorate while pain perception persists.

Apart from these external stimulants, chemical nociceptors have the capacity to detect endogenous ligands, and certain fatty acid amines that arise from changes in internal tissues.

[10] Although each nociceptor can have a variety of possible threshold levels, some do not respond at all to chemical, thermal or mechanical stimuli unless injury actually has occurred.

Afferent nociceptive fibers (those that send information to, rather than from the brain) travel back to the spinal cord where they form synapses in its dorsal horn.

The brain can request the release of specific hormones or chemicals that can have analgesic effects which can reduce or inhibit pain sensation.

[13] This effect of descending inhibition can be shown by electrically stimulating the periaqueductal grey area of the midbrain or the periventricular nucleus.

In turn the nucleus raphe magnus projects to the substantia gelatinosa region of the dorsal horn and mediates the sensation of spinothalamic inputs.

Nociceptor sensitivity is modulated by a large variety of mediators in the extracellular space, such as toxic and inflammatory molecules.

Normally hyperalgesia ceases when inflammation goes down, however, sometimes genetic defects and/or repeated injury can result in allodynia: a completely non-noxious stimulus like light touch causes extreme pain.

With this situation, surviving dorsal root axons of the nociceptors can make contact with the spinal cord, thus changing the normal input.

They are classified as either peptidergic or nonpeptidergic nociceptors, each of which express a distinct repertoire of ion channels and receptors.

On the contrary, the peptidergic nociceptors continue to use TrkA, and they express a completely different type of growth factor.

[21] Although these neurons may have pathways and relationships to the central nervous system that are different from those of mammalian nociceptors, nociceptive neurons in non-mammals often fire in response to similar stimuli as mammals, such as high temperature (40 degrees C or more), low pH, capsaicin, and tissue damage.