Definition

Acute pain is defined as “pain of recent onset and probable limited duration. It usually has an identifiable temporal and causal relationship to injury or disease” (Ready and Edwards 1992). The perception of acute pain requires transduction of noxious mechanical, thermal or chemical stimuli by nociceptive neurons, integration and modulation at the level of the spinal cord and ultimately transmission to cortical centres.

Characteristics

Peripheral Nociception

Nociceptors in the skin and other deeper somatic tissues such as periosteum are morphologically free nerve endings or simple receptor structures. A noxious stimulus activates the nociceptor depolarising the membrane via a variety of stimulus specific transduction mechanisms. C polymodal nociceptors are the most numerous of somatic nociceptors and respond to a full range of mechanical, chemical and thermal noxious stimuli. Polymodal nociceptors are coupled to unmyelinated C fibres. Electrophysiological activity in these slow conduction C fibres is characteristically perceived as dull, burning pain. Faster conducting Aδ fibres are coupled to more selective thermal and mechano-thermal receptors considered responsible for the perception of sharp or “stabbing” pain (Julius and Basbaum 2001).

Inflammatory Induced Peripheral Sensitization

A complex interaction of molecules produced during the inflammation acting on nociceptors results in functional, morphological and electrophysiological changes causing “primary hyperalgesia”. Nociceptors are sensitised due to changes in the absolute numbers of Na+ and K+ channels and their relative “open-closed” kinetics. This results in neuronal activation in response to innocuous stimuli and spontaneous ectopic discharges. Inflammatory mediators also act to increase the activity of “silent” nociceptors normally unresponsive to even noxious stimuli. There is an increase in many ion channel subtypes, (particularly the tetrodotoxin (TTX) resistant Na+ channel) both on the axon and also in the dorsal root ganglion (DRG) (Kidd and Urban 2001). There is up-regulation of receptor expression, including substance P and brain derived growth factor (BDGF). Morphological changes including sprouting of unmyelinated nerve fibres have also been identified.

Spinal Cord Integration

The majority of somatic nociceptive neurons enter the dorsal horn spinal cord at their segmental level. A proportion of fibres pass either rostrally or caudally in Lissauer's tract. Somatic primary afferent fibres terminate predominantly in laminas I (marginal zone) and II (substantia gelatinosa) of the dorsal horn where they synapse with projection neurons and excitatory/inhibitory interneurons. Some Aδ fibres penetrate more deeply into lamina V. Projection neurons are of three types classified as nociceptive specific (NS), low threshold (LT) and wide dynamic range neurons (WDR). The NS neurons are located predominantly in lamina I and respond exclusively to noxious stimuli. They are characterised by a small receptive field. LT neurons, which are located in laminae III and IV, respond to innocuous stimuli only. WDR neurons predominate in lamina V (also in I), display a large receptive field and receive input from wide range of sensory afferents (C, Aβ) (Parent 1996).

Spinal Modulation and Central Sensitisation

Glutamate and aspartate are the primary neurotransmitters involved in spinal excitatory transmission. Fast post-synaptic potentials generated via the action of glutamate on AMPA receptors are primarily involved in nociceptive transmission (Smullen et al. 1990). Prolonged C fibre activation facilitates glutamate-mediated activation of NMDA receptors and subsequent prolonged depolarization of the WDR neuron (termed “wind-up”). This is associated with removal of a Mg+ plug from the NMDA-gated ion channel. The activation of this voltage gated Ca+ channel is associated with an increase in intracellular Ca+ and up-regulated neurotransmission (McBain and Mayer 1994). The peptidergic neurotransmitters substance P and calcitonin G related peptide (CGRP) are co-produced in glutaminergic neurons and released with afferent stimulation. These transmitters appear to play a neuromodulatory role, facilitating the action of excitatory amino acids. A number of other molecules including glycine, GABA, somatostatin, endogenous opioids and endocannabinoids play modulatory roles in spinal nociceptive transmission (Fürst 1999).

Projection Pathways

Nociceptive somatic input is relayed to higher cerebral centres via three main ascending pathways the spinothalamic, spinoreticular and spinomesencephalic tracts (Basbaum and Jessel 2000). The spinothalamic path originates in laminae I and V–VII and is composed of NS and WDR neuron axons. It projects to thalamus via lateral (neospinothalamic tracts), and medial or paleospinothalamic tracts. The lateral tract passes to the ventro-postero-medial nucleus and subserves discriminative components of pain, while the medial tract is responsible for the autonomic and emotional components of pain. Additional fibres pass to reticular activating system, where they are associated with the arousal response to pain and the periaqueductal grey matter (PAG) where ascending inputs interact with descending modulatory fibres. The spinoreticular pathway originates in laminae VII and VIII and terminates on the medial medullary reticular formation. The spinomesencephalic tract originates in laminae I and V and terminates in the superior colliculus. Additional projections pass to the mesencephalic PAG. It appears that this pathway is not essential for pain perception but plays an important role in the modulation of afferent inputs.

Cortical Representation

Multiple cortical areas are activated by nociceptive afferent input including the primary and secondary somatosensory cortex, the insula, the anterior cingulate cortex and the prefrontal cortex. Pain is a multidimensional experience with sensory-discriminative and affective-motivational components. Advances in functional brain imaging have allowed further understanding of the putative role of cortical structures in the pain experience (Treede et al. 1999).

  1. 1.

    Localization

    1. a)

      primary somatosensory cortex

    2. b)

      secondary somatosensory cortex

    3. c)

      insula

  1. 2.

    Intensity

    1. a)

      prefrontal cortex

    2. b)

      right posterior cingulate cortex

    3. c)

      brainstem

    4. d)

      periventricular grey matter

  1. 3.

    Affective Component

    1. a)

      left anterior cingulate cortex

  1. 4.

    Threshold

    1. a)

      cingulate cortex

    2. b)

      left thalamus

    3. c)

      frontal inferior cortex