Laminae, pain

Fig. 4.1 Hypothetical model of pathogenesis of pain in DSP. (1) Injury of peripheral nerve fibers due to multifocal inflammation and secreted macrophage activation products results in abnormal spontaneous activity of neighboring uninjured nociceptive fibers ( peripheral sensitization ). (2) Furthermore, the aberrant inflammatory response in DRG leads to alterations in neuronal sodium and calcium channel expression and ectopic impulse generation. (3) This results in central remodeling within the dorsal horn due to A-fiber sprouting and synaptic formation with pain fibers in lamina 11, and maintenance of neuropathic pain ( central sensitization ). Reproduced with permission from (Keswani et al. 2002)...

D. Schulte and J. Millar, The effects of high- and low-intensity percutaneous stimulation on nitric oxide levels and spike activity in the superficial laminae of the spinal cord. Pain 103, 139-150 (2003). 

A5 and C primarily project to lamina II and V of the dorsal horn, where they synapse onto local interneurons or directly onto upward-projecting neurons (figure 8.1). These primary afferents release a number of neurotransmitters to relay pain, including glutamate, aspartate, substance P, neurokinin A and B, and calcitonin gene-related peptide (table 8.1). NMDA, non-NMDA and neurokinin receptors are involved in re-... 

N-type Ca2+ channels for instance are located at presynaptic termini of neurons where they are directly involved in the regulation of neurotransmitter release. Staining of the dorsal laminae of the rat spinal cord revealed a complementary distribution of class A and class B Ca2+ channels in nerve terminals in the deeper versus the superficial laminae. Many of the nerve terminals immunoreactive for class B N-type Ca2+ channels also contain substance P, an important neuropeptide in pain pathways, suggesting the N-type Ca2+ channels are predominant at synapses that carry nociceptive information to the spinal cord (Westernbroek etal., 1998). 

Mechanism of action Opioids exert their major effects by interacting with opioid receptors in the CNS and the gastrointestinal tract. Opioids cause hyperpolarization of nerve cells, inhibition of nerve firing, and presynaptic inhibition of transmitter release. Morphine acts at k receptors in lamina I and II of the substantia gelatinosa of the spinal cord, and decreases the release of substance P, which modulates pain perception in the spinal cord. Morphine also appears to inhibit the release of many excitatory transmitters from nerve terminals carrying nociceptive (painful) stimuli. 

Gao L, Yu LC (2004) Involvement of opioid receptors in the oxytodn-induced antinociception in the central nervous system of rats. Regul Pept 120 53-58 Garden LR, Ibrahim M, Wang R, Wang Z, Ossipov MH, Malan TP Jr, Porreca F, Lai J (2004) Mouse strains that lack spinal dynorphin upregulation after peripheral nerve injury do not develop neuropathic pain. Neurosdence 123 43-52 Garraway SM, Anderson AJ, MendeU LM (2005) BDNF-induced fadlitation of afferent-evoked responses in lamina II neurons is reduced tifter neonattil spinal cord contusion injury. J Neurophysiol 94 1798-1804... 

Because of the efficacy of intrathecal cannabinoids in various pain models, it is not surprising that moderate levels of CBi receptor are found in the regions of the spinal cord associated with analgesia. In particular, the superficial layers of the dorsal horn, the dorsolateral funiculus, and lamina X all have moderate levels of CBi receptor (Farquhar-Smith et al. 2000). Cannabinoids inhibit glutamate release from afferents in lamina I of the dorsal horn in a CBi receptor-dependent fashion (Jennings et al. 2001 Morisset and Urban 2001). Providing anatomical support for these functional studies, CBi receptors are found in the dorsal horn in a characteristic twin band corresponding to lamina I and the inner portion of lamina II (Farquhar-Smith et al. 2000). 

There is considerable support for localization of CBRs in rat spinal cord postsynaptic to primary afferents at both light and electron microscope levels. Direct evidence for postsynaptic localization of CBi in spinal dorsal horn is derived from the observation that intrinsic excitatory interneurons in lamina Hi that expressed protein kinase C isoform y showed high levels of colocalization with CBi (Farquhar-Smith et al. 2000) this pattern may suggest an anatomical basis for the efficacy of cannabinoids in ameliorating inflammatory and neuropathic pain (Bridges et al. 2001 Fox et al. 2001 Herzberg et al. 1997 Malmberg et al. 1997 Mao et al. 2000). 

Nociceptive transmission takes place in A5 and C-afferent nerve fibers. Stimulation of large-diameter, sparsely myelinated A5 fibers evokes sharp, well-localized pain, whereas stimulation of unmyelinated, small-diameter C fibers produces dull, aching, and poorly localized pain. These afferent, nociceptive pain fibers synapse in various layers (laminae) of the spinal cord s dorsal hom, releasing a... 

Malmalbo — Malmal means rotten. The taste and smell of this cultivar are reminiscent of rotten pig meat. It produces a highly potent beverage, and drinkers experience its effects over two or three days. The cultivar is fairly uncommon and is used mainly in traditional medicine to relieve rheumatic pains. Its stems are paler than those of borogu and its leaves smell like those of melmel or bukulit. The laminae are a darker green than those of borogu. 

Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424 938-942... 

The most common type of injury due to combined tension and extension of the cervical spine is the whiplash syndrome. However, a large majority of such injuries involve the soft tissues of the neck, and the pain is believed to reside in the joint capsules of the articular facets of the cervical vertebrae [Wallis et al., 1997]. In severe cases, teardrop fractures of the anterosuperior aspect of the vertebral body can occur. Alternately, separation of the anterior aspect of the disk from the vertebral endplate is known to occur. More severe injuries occur when the chin impacts the instrument panel or when the forehead impacts the windshield. In both cases, the head rotates rearward and applies a tensile and bending load on the neck. In the case of windshield impact by the forehead, hangman s fracture of C2 can occur. Garfin and Rothman [1983] suggested that it is caused by spinal extension combined with compression on the lamina of C2, causing the pars to fracture. 

Epidural hydromorphone s primary site of action is at endogenous opioid receptors located on neurons in lamina 1-11 (substantia gelatinosa) and lamina V of the spinal dorsal horn. Following epidural administration, hydromorphone enters the spinal cord and activates pre- and postsynaptic mu receptors and suppresses pain transmission. Systemic absorption and activation of central opioid receptors may provide additional analgesia. Hydromorphone is not particularly hydrophilic, and rostral migration in CSF is of lower magnitude than that observed with morphine. Rostral spread of hydromorphone may result in undesirable side effects such as pruritus, nausea and vomiting, and sedation. Epidural hydromorphone is associated with dose-dependent reductions in respiratory rate and minute ventilation however, unlike morphine, delayed-onset respiratory depression is less likely to occur [3,4]. 

Ziconotide is a synthetic equivalent of a naturally occurring conopeptide found in the piscivorous marine snail. Conus magus. Ziconotide binds to N-type volt-age-gated calcium channels located on the primary nociceptive (Ap and C) afferent nerves in the superficial layers (Rexed laminae I and II) of the dorsal horn in the spinal cord. It was approved for use in the USA in 2004 for control of severe chronic pain. 

It is well known that peripheral nerve injury or inflammatory states induce neuronal plastic changes in the spinal cord. These plasticity changes are responsible for the production and maintainance of persistent pain states, allodynia, and hyperalgesia occurring in both affected areas (primary sensitization) and non-affected areas (secondary sensitization). In inflammatory states, the NC OF FQ system is up-regulated [4]. This is reflected by increased NC levels and binding in the spinal cord, specifically at the level of the dorsal 51Q horns - mainly limited to the superficial laminae I and II. Inflammatory states also induce the expression of... 

Fig. 9.3a-d. a A 58-year-old male patient with renal cell cancer and a symptomatic metastasis to the fifth lumbar vertebra. Note that the posterior lamina of the vertebra is already penetrated, b The coronal re-formation displays the total cranio-caudal extent, c The lamina of the pedicle could be passed by the umbrella-like electrode and the tines could be deployed within the tumoral cavity. Under conscious sedation without any neurological sensations the ablation procedure was performed with 10 W over 10 min until the impedance rose significantly, aborting the energy delivery, d Subsequently, in the same session, a vertebroplasty needle was placed into the tumor cavity and 2.5 ml of PMMA cement were injected under CT-fluoroscopic guidance. Within 24 h the patient was free of pain and presented during the follow-up period of 30 months with no tumor or pain recurrence... 

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