Pain basics – explaining how the CNS and the brain are involved

Pain becomes conscious in the brain, more precisely in the cerebral cortex. Before the pain signal can be perceived it has made its way through the body from the periphery to the central nervous system (CNS).

The central and peripheral nervous system can be considered as a network via which the pain stimulus is conveyed within the body. The nerve cells that convey sensory impulses from the periphery to the CNS are described as afferent (ascending to the CNS). Nerve cells that transmit signals from the CNS to the muscles, glands and organs are referred to as efferent neurons (descending from the CNS).


Pain processing - Basics



In contrast to pain, which is defined as a subjective sensorial or emotional event, nociception means the reception, transmission and central nervous processing of noxious (tissue-damaging or potentially tissue-damaging) stimuli. The painful stimulation referred to as nociceptive stimulation activates specific pain receptors called "nociceptors". Nociceptors are free nerve endings excited by damaging stimuli arising from various causes. Most nociceptors are polymodal, i.e. they react to several different types of stimuli, e.g. thermal, mechanical and chemical stimuli. They are present in large numbers in the skin, but they are also found in the muscles, periosteum, the capsules of internal organs and the walls of vessels and hollow organs. There are no nociceptors in the brain.


Spinal Cord

The cord conveys the 31 spinal nerve pairs of the peripheral nervous system, as well as central nervous system pathways that innervate skeletal muscles. Inside the spinal cord, there is grey matter surrounded by white matter. The dorsal horn is the dorsal section of the grey substance of the spinal cord.

The cells of the dorsal horn of the spinal cord are the first processing level for the pain stimuli. Sensory nerve fibres coming from the periphery end here and neural impulses are switched to the second sensory neuron at excitatory synapses ascending to higher centres of the brain (afferent/ascending pathways).

In the other direction, motoneural responses and pain modulating inhibitory signals coming from the higher levels of the CNS are descending the spinal cord (efferent/descending pathways).


Ascending pathways

The pain system involves a set of ascending pathways that convey nociceptive information from peripheral nociceptors via neuronal tracts of the spinal cord to higher levels of the CNS. When free nerve endings are excited, their membrane potential changes (transduction) and is converted into an action potential (transformation).

Afferent (i.e. ascending) A-delta and C fibres of the periphery transmit the pain stimulus via action potentials to the dorsal horn of the spinal cord. The transmission of nociceptive information from the first to the second neuron takes place at the synapsis by means of excitatory neurotransmitters. The neurotransmitters bind post-synaptically to specific receptors and produce an action potential, which is transmitted to the brain.



Pain processing - Brain

Different structures of the brain are involved in processing the pain signal and pain perception. The perception of pain does not only depend on the somatic input, but also on individual factors such as ethnic origin, education and socio-cultural environment and also on psychological factors. The image displays the main anatomical entities of the brain.

Concerning pain, the following structures are of special interest:


  • Cerebral cortex is the part of the brain where the perception as pain takes place.
  • Periaquaeductal grey (PAG; also called the "central grey") is the midbrain grey substance that is located around the cerebral aqueduct. It plays a role in the descending modulation of pain and in defensive behaviour.
  • Thalamus is a symmetric part of the brain. It constitutes the main part of the diencephalon. The thalamus acts as a relay station: dissemination of the signals to various areas of the brain, including transmission to the cerebral cortex.
  • Limbic system is a regulation centre of the pain threshold and of emotional reactions.


Descending Inhibition

Neuronal centres of the cortex and subcortical areas of the brain respond to incoming (ascended) pain signals and can modulate pain signals by activating inhibitory descending (efferent) pathways. The impulses (again, action potentials) descend to the dorsal horn of the spinal cord (where respective painful stimuli are transmitted to the second order neuron). Activated inhibitory interneurons release inhibitory neurotransmitters such as noradrenaline and serotonine which modulate ascending pain transmission. Also endorphins are involved in inhibitory modulation of pain signals.