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Anatomy and physiology of pain

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A comprehensive guide to the anatomy and physiology of pain management

Many nurses have a poor understanding of pain and its management, which can result in failure to treat pain effectively. An insight into the anatomy and physiology of pain is essential to increase nurses’ understanding of what it is and how interventions can help to manage it. This section outlines the basic anatomy and physiology of pain.

Acute pain

Acute pain is a physiological response that warns us of danger. The process of nociception describes the normal processing of pain and the responses to noxious stimuli that are damaging or potentially damaging to normal tissue. There are four basic processes involved in nociception (McCaffery and Pasero, 1999). These are;

  • transduction;
  • transmission;
  • perception;
  • modulation.

Transduction of pain

Transduction begins when the free nerve endings (nociceptors) of C fibres and A-delta fibres of primary afferent neurones respond to noxious stimuli. Nociceptors are exposed to noxious stimuli when tissue damage and inflammation occurs as a result of, for example, trauma, surgery, inflammation, infection, and ischemia.

The nociceptors are distributed in the;

  • somatic structures (skin, muscles, connective tissue, bones, joints);
  • visceral structures (visceral organs such as liver, gastro-intestinal tract).
  • The C fibre and A-delta fibres are associated with different qualities of pain. These are listed in table 1.

Table 1. Characteristics and functions of C fibre and A-delta fibres

C fibres A-delta fibres


  • Primary afferent fibres
  • Small diameter
  • Unmyelinated
  • Slow conducting

Receptor type:

  • Polymodal respond to more than one type of noxious stimuli:
  • Mechanical
  • Thermal
  • Chemical

Pain quality:

  • Diffuse
  • Dull
  • Burning
  • Aching
  • Referred to as ‘slow’ or second’ pain


  • Primary afferent fibres
  • Large diameter
  • Myelinated
  • Fast conducting

Receptor type:

  • High-threshold mechanoreceptors respond mechanical stimuli over a certain intensity.

Pain quality:

  • Well-localised
  • Sharp
  • Stinging
  • Pricking
  • Referred to as ‘fast’ or ‘first’ pain

Noxious stimuli and responses

There are three categories of noxious stimuli:

  • mechanical (pressure, swelling, abscess, incision, tumour growth);
  • thermal (burn, scald);
  • chemical (excitatory neurotransmitter, toxic substance, ischaemia, infection).

The cause of stimulation may be internal, such as pressure exerted by a tumour or external, for example, a burn. This noxious stimulation causes a release of chemical mediators from the damaged cells including:

  • prostaglandin;
  • bradykinin;
  • serotonin;
  • substance P;
  • potassium;
  • histamine.

These chemical mediators activate and/or sensitise the nociceptors to the noxious stimuli. In order for a pain impulse to be generated, an exchange of sodium and potassium ions (de-polarisation and re-polarisation) occurs at the cell membranes. This results in an action potential and generation of a pain impulse.

Transmission of pain

The transmission process occurs in three stages. The pain impulse is transmitted:

  • from the site of transduction along the nociceptor fibres to the dorsal horn in the spinal cord;
  • from the spinal cord to the brain stem;
  • through connections between the thalamus, cortex and higher levels of the brain.

The C fibre and A-delta fibres terminate in the dorsal horn of the spinal cord. There is a synaptic cleft between the terminal ends of the C fibre and A-delta fibres and the nociceptive dorsal horn neurones (NDHN). In order for the pain impulses to be transmitted across the synaptic cleft to the NDHN, excitatory neurotransmitters are released, which bind to specific receptors in the NDHN. These neurotransmitters are:

  • adenosine triphosphate;
  • glutamate;
  • calcitonin gene-related peptide;
  • bradykinin;
  • nitric oxide;
  • substance P.

The pain impulse is then transmitted from the spinal cord to the brain stem and thalamus via two main nociceptive ascending pathways. These are the spinothalamic pathway and the spinoparabrachial pathway.

The brain does not have a discrete pain centre, so when impulses arrive in the thalamus they are directed to multiple areas in the brain where they are processed.

Perception of pain

Perception of pain is the end result of the neuronal activity of pain transmission and where pain becomes a conscious multidimensional experience. The multidimensional experience of pain has affective-motivational, sensory-discriminative, emotional and behavioural components.
When the painful stimuli are transmitted to the brain stem and thalamus, multiple cortical areas are activated and responses are elicited.

These areas are:

  • The reticular system: This is responsible for the autonomic and motor response to pain and for warning the individual to do something, for example, automatically removing a hand when it touches a hot saucepan. It also has a role in the affective-motivational response to pain such as looking at and assessing the injury to the hand once it has been removed form the hot saucepan.
  • Somatosensory cortex: This is involved with the perception and interpretation of sensations. It identifies the intensity, type and location of the pain sensation and relates the sensation to past experiences, memory and cognitive activities. It identifies the nature of the stimulus before it triggers a response, for example, where the pain is, how strong it is and what it feels like.
  • Limbic system: This is responsible for the emotional and behavioural responses to pain for example, attention, mood, and motivation, and also with processing pain and past experiences of pain.

Modulation of pain

The modulation of pain involves changing or inhibiting transmission of pain impulses in the spinal cord. The multiple, complex pathways involved in the modulation of pain are referred to as the descending modulatory pain pathways (DMPP) and these can lead to either an increase in the transmission of pain impulses (excitatory) or a decrease in transmission (inhibition).

Descending inhibition involves the release of inhibitory neurotransmitters that block or partially block the transmission of pain impulses, and therefore produce analgesia. Inhibitory neurotransmitters involved with the modulation of pain include:

  • endogenous opioids (enkephalins and endorphins);
  • serotonin (5-HT);
  • norepinephirine (noradrenalin);
  • gamma-aminobutyric acid (GABA);
  • neurotensin;
  • acetylcholine;
  • oxytocin.

Endogenous pain modulation helps to explain the wide variations in the perception of pain in different people as individuals produce different amounts of inhibitory neurotransmitters. Endogenous opioids are found throughout the central nervous system (CNS) and prevent the release of some excitatory neurotransmitters, for example, substance P, therefore, inhibiting the transmission of pain impulses.

Chronic pain

Chronic pain can be a major problem for some people and affect their quality of life. It can be caused by alterations in nociception, injury or disease and may result from current or past damage to the peripheral nervous system (PNS), CNS, or may have no organic cause (Calvino and Grilo, 2006).

Pathophysiology of chronic pain

The exact mechanisms involved in the pathophysiology of chronic pain are complex and remain unclear. It is believed that following injury, rapid and long-term changes occur in parts of the CNS that are involved in the transmission and modulation of pain (nociceptive information) (Ko and Zhuo, 2004).

A central mechanism in the spinal cord, called ‘wind-up’, also referred to as hypersensitivity or hyperexcitability, may occur. Wind-up occurs when repeated, prolonged, noxious stimulation causes the dorsal horn neurones to transmit progressively increasing numbers of pain impulses.

The patient can feel intense pain in response to a stimulus that is not usually associated with pain, for example, touch. This is called allodynia.

This abnormal processing of pain within the PNS and CNS may become independent of the original painful event. In some cases, for example, amputation, the original injury may have occurred in the peripheral nerves, but the mechanisms that underlie the phantom pain are generated in both the PNS and the CNS.

Neuropathic pain

Neuropathic pain can be defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system resulting from;

  • trauma, for example, complex regional pain syndrome, chronic post-surgical pain;
  • infection, for example, post-herpetic neuralgia;
  • ischaemia, for example, diabetic neuropathy;
  • cancer;
  • chemically induced, for example, as a result of chemotherapy (Farquhar-Smith, 2007).

Some types of neuropathic pain may develop when the PNS has become damaged, causing the pain fibres to transmit pain impulses repetitively and become increasingly sensitive to stimuli. Neuroplasticity may also develop and is characterised by abnormal neuronal sprouting in the PNS and within the dorsal horn of the spinal cord. This sprouting may result in additional generation of and increased transmission of pain impulses.

Characteristics of neuropathic pain

Neuropathic pain is distinctly different from nociceptive pain and is described as:

  • burning;
  • dull;
  • aching;
  • tingling;
  • like an electric shock;
  • shooting.

The types of neuropathic pain are divided into categories and these are listed in Fig 1.


This anatomy and physiology section has briefly illustrated the processes that are involved in generating the sensation of pain. This provided the basis for the assessment of pain and the selection of appropriate interventions for managing this pain effectively.

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