Nociceptive pain is the ‘normal’ pain pathway that occurs in response to tissue injury or damage. Figure 10.1 demonstrates the normal pathway for sensory input and motor output through the spinal cord. As an example, if a person touches a hot plate, this causes pain and this sensory input travels through the spinal cord to the brain and the motor output. In response, the person withdraws their hand from the painful heat source.

The pain pathway consists of four components: transduction, transmission, perception and modulation. Nociceptors are free nerve endings found at the end of pain neurones. Nociceptive primary afferents are widely distributed throughout the body (skin, muscle, joints, viscera and meninges) and comprise both medium‐diameter lightly myelinated A delta fibres and small‐diameter, slow‐conducting unmyelinated C fibres (Schug et al. [166]). Nociceptors respond to noxious thermal stimuli (heat and cold) and mechanical stimuli (stretching, compression and infiltration) and to the chemical mediators released as part of the inflammatory response to tissue injury (Steeds [172]). These chemical mediators include prostaglandins, bradykinin, histamine, hydrogen ions (protons), 5‐hydroxytryptamine (5‐HT), cytokines and leukotrienes (Steeds [172]). As a result of this stimulation process, an action potential is generated in the nerve (transduction).

The pain signal is then transmitted along the peripheral nervous system (A delta and C fibres) to the central nervous system, arriving at the dorsal horn of the spinal cord. Neurotransmitters are released to allow the pain signal to be transmitted from the endings of the peripheral nerves to the nociceptors in the dorsal horn and onwards through the central nervous system. These include substance P, galanin, glutamate, GABA (γ‐aminobutyric acid), cholecystokinin and others (Steeds [172]). The message is then transmitted to the brain, where perception of the pain occurs (transmission). Perception is the end result of the neuronal activity of pain transmission. The perception of pain includes behavioural, psychological and emotional components as well as physiological processes.

Modulation occurs when the transmission of pain impulses in the spinal cord is changed or inhibited. Modulatory influences on pain perception are complex, involving a gating system that is linked to a descending modulatory pathway. Modulation can occur as a result of a natural release of inhibitory neurotransmitter chemicals (noradrenaline and 5‐HT) that inhibit transmission of pain impulses and therefore produce analgesia. Other interventions, including distraction, relaxation, sense of wellbeing, heat and cold therapy, massage and TENS, can also help to modulate pain perception. Analgesic medications work by inhibiting some of the chemicals involved in pain transduction and transmission and thus modulating pain perception (Figure 10.2). Pain signals can also be increased by certain factors such as anxiety, fear, and low mood or depression.

Neuropathic pain is not pain that originates as part of ‘normal’ pain pathways. It has been described as pain related to abnormal processing within the nervous system. Although distinct definitions of neuropathic pain have been used over the years, its most recent and widely accepted definition is pain or abnormal sensation caused by a primary lesion or disease of the nervous system (Colloca et al. [42]). This can consist of motor, sensory or autonomic dysfunction (Steeds [172]).

The somatosensory system allows for the perception of touch, pressure, pain, temperature, position, movement and vibration. The somatosensory nerves arise in the skin, muscles, joints and fascia and include thermoreceptors, mechanoreceptors, chemoreceptors, pruriceptors and nociceptors, which send signals to the spinal cord and eventually to the brain for further processing. Lesions or diseases of the somatosensory nervous system can lead to altered and disordered transmission of sensory signals into the spinal cord and the brain (Colloca et al. [42]).

Common conditions associated with neuropathic pain include postherpetic neuralgia, trigeminal neuralgia, painful radiculopathy, diabetic neuropathy, HIV infection, leprosy, amputation, peripheral nerve injury pain, stroke (in the form of central post‐stroke pain), trauma (such as surgery or acute injury), and nerve compression or infiltration (such as degenerative joint and spinal disease or tumours) (Colloca et al. [42], Mann [103]).

The following theories are currently thought to explain the mechanisms by which neuropathic pain is generated and maintained (Baron et al. [7], Nickel et al. [128]):

The nervous system changes its structure and function in response to the input it receives – in other words, it is plastic. Plasticity is evident at all levels from the nociceptors to the brain (cortex). These mechanisms result in increased activity or transmission of pain signals despite less input from the peripheral nervous system. Pain may be spontaneous, may be triggered by non‐painful stimuli such as touch (allodynia) or may consist of an exaggerated pain response (hyperalgesia). Patients may also experience non‐painful sensations such as pins and needles and tingling (paraesthesia).