Pain and Analgesia


The accepted definition of pain is ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. Analgesia is the alleviation or the absence of pain. Damaging or threatening physiological changes activate sensory neurons that support homeostasis, which drive autonomic, motoric, immune, behavioural, emotional and mnemonic responses. In humans, nociceptive neurons directly activate limbic sensory (insula) and limbic motor (cingulate) cortices as well as somatosensory cortices; they also produce glial and other immune (inflammatory) and stress‐related (sympathetic) responses, which can lead to chronic pathological pain, considered by many to be a disease state. The pharmacologies of these overlapping systems involve numerous common agents, such as glutamate, adenosine, substance P, catecholamines, opioids, cannabinoids, prostanoids and so on, but accelerating advances in technology and in our knowledge of these systems suggest that selectively analgesic pathways and agents may be found that could underpin clinically useful therapies for chronic pain.

Key Concepts:

  • Small‐diameter primary afferent fibres that innervate all tissues of the body (except the brain itself) and signal damaging or threatening physiological changes (as the sensory component of homeostasis) underlie pain sensation.

  • In humans, pain is associated with activation of limbic sensory (insula) and limbic motor (cingulate) cortices, as well as the somatosensory cortices; the first two regions may represent the feeling and the motivation (unpleasantness) of pain, respectively.

  • Primary afferent neurotransmitters are most commonly glutamate and adenosine. A host of peptides, growth factors and other neuromodulatory agents may also be co‐released. These agents work together to effects changes on other neurons and on glia.

  • Activation of primary afferents contributes to (neurogenic) inflammation via release of neurotransmitters/neuromodulators from peripheral terminals that activate other nociceptors as well as cause increased permeability and vasodilation of local blood vessels.

  • Hyperalgesia, that is, pain caused by normally nonpainful events as well as increased responses to painful events, is produced by activation of local immune (glial) elements, sensitisation of peripheral and central neurons, and responsiveness to low‐threshold (tactile) A‐beta and C fibres.

  • Endogenous anti‐nociceptive inhibitory systems underlie the effects of vibration, cooling and cardiorespiratory events on pain and are supported by aminergic, opiatergic and cannabinoid agents.

  • Chronic, pathological pain (lasting longer than 3–6 months) can result if injury or disease alters the balance of the homeostatic and immune systems to produce a persistent ‘pain memory’. Conversely, intense, unremitting pain can produce homeostatic, emotional, nutritional and sleep imbalances that can be fatal.

  • Opiates including morphine and the endogenous peptides inhibit nociceptive activity in the periphery and at all levels of the neuraxis. They are more effective for inflammatory pain than for pain resulting from injury to the nervous system. Opiate effects can be heightened by local anesthetics and adrenergic agonists.

Keywords: nociception; injury; inflammation; hyperalgesia; spinothalamic

Figure 1.

The anatomy of the spinal cord at the cervical level depicting the Aα, β, δ and C fibres and their potential target regions mediating the nociception. MDvc, ventral caudal part of the medial dorsal nucleus; VPI, ventral posterior inferior nucleus; VMpo, posterior part of the ventral medial nucleus; PAG, periaqueductal grey; PB, parabrachial nucleus; IML, intermediolateral cell column; HPC, polymodal nociceptive cell (‘heat, pinch and cold’); NS, nociceptive‐specific cell and STT, spinothalamic tract.



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Craig, AD, and Sorkin, LS(Mar 2011) Pain and Analgesia. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0000275.pub3]