doi:10.1093/bja/aen088 Advance Access publication April 15, 2008
REVIEW ARTICLES Spinal cord mechanisms of pain
R. D’Mello* and A. H. Dickenson
Department of Pharmacology, University College London, Gower Street, London WC1E 6BT, UK
*Corresponding author. E-mail: r.d’email@example.com
The spinal cord is the ﬁrst relay site in thetransmission of nociceptive information from the periphery to the brain. Sensory signals are transmitted from the periphery by primary afferent ﬁbres into the dorsal horn of the spinal cord, where these afferents synapse with intrinsic spinal dorsal horn neurones. Spinal projection neurones then convey this information to higher centres in the brain, where non-noxious and noxious signals can beperceived. During nociceptive transmission, the output of the spinal cord is dependent on various spinal mechanisms which can either increase or decrease the activity of dorsal horn neurones. Such mechanisms include local excitatory and inhibitory interneurones, N-methyl-D-aspartate receptor activation, and descending inﬂuences from the brainstem, which can be both inhibitory and excitatory in nature.After nerve injury or conditions of inﬂammation, shifts can occur in these excitatory and inhibitory mechanisms which modulate spinal excitability, often resulting in the heightened response of dorsal neurones to incoming afferent signals, and increased output to the brain, a phenomenon known as central sensitization. In this review, we consider the ways in which spinal cord activity may be alteredin chronic pain states. In addition, we discuss the spinal mechanisms which are targeted by current analgesics used in the management of chronic pain. Br J Anaesth 2008; 101: 8 –16 Keywords: analgesics non-opioid; pain; spinal cord
Downloaded from http://bja.oxfordjournals.org/ at Universidade Federal do Rio de Janeiro on March 29, 2012
According to the International Association for the Studyof Pain (IASP), pain is deﬁned as ‘an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage’. This deﬁnition reminds us that pain involves a signiﬁcant psychological component which can alter its perception and therefore, undergoes extensive processing through the nervous system, and particularly in the brain. Thisaccount considers the ways in which the spinal cord, the ﬁrst relay in the pathways from the periphery to the brain, can be sensitized by noxious stimuli, and thus allows a minor peripheral input to now be ampliﬁed. In addition, we will explore the ways in which current and future drugs may target spinal mechanisms in the treatment of chronic pain states.
Peripheral mechanisms of sensorytransmission
The sensory experience begins in the periphery, where the peripheral terminals of primary afferent ﬁbres respond to a myriad of stimuli and translate this information into the dorsal horn of the spinal cord, where the central ends of these ﬁbres terminate (Fig. 1). There are three main types of sensory ﬁbre in the peripheral nervous system, Ab-ﬁbres,
Ad-ﬁbres, and C-ﬁbres. Each hasdifferent properties allowing them to respond to and transmit different types of sensory information. Ab-ﬁbres are large in diameter and highly myelinated, thus allowing them to quickly conduct action potentials from their peripheral to central terminals. These ﬁbres have low activation thresholds and normally respond to light touch and are responsible for conveying tactile information. Ad-ﬁbres aresmaller in diameter and thinly myelinated, making them slower-conducting than Ab-ﬁbres, and they also possess higher activation thresholds. They respond to both thermal and mechanical stimuli. C-ﬁbres are the smallest type of primary afferents and are unmyelinated, thus making them the slowest conducting. They have the highest thresholds for activation and therefore detect selectively nociceptive or...