The Initial Injury

MCP1/CCR2 by DRG neurons occurs some days following the initial injury, it is also likely that excitation produced in this fashion may be more important for the maintenance of chronic pain rather than its initiation. Thus, according to this view the major site of action of MCP-1 is within the DRG rather than in the SC. 

Autolysis of the pancreas can occur when zymogens are activated in the pancreas before being released into the duodenum. Acute pancreatitis can result from the initial injury to the zymogen-producing cells, which is followed by neutrophil invasion of the pancreas, and that ends in further activation of enzymes within the pancreas. This cascade of events can be destructive to the pancreas and harmful to the patient. 

Skeletal muscle spasms are used to describe the increased tension often seen in skeletal muscle after certain musculoskeletal injuries and inflammation (muscle strains, nerve root impingements, etc.) occur.20,96 This tension is involuntary, so the patient is unable to relax the muscle. Spasms differ from spasticity because spasms typically arise from an orthopedic injury to a musculoskeletal structure or peripheral nerve root rather than an injury to the CNS. Likewise, muscle spasms are often a continuous, tonic contraction of specific muscles rather than the velocity-dependent increase in stretch reflex activity commonly associated with spasticity. The exact reasons for muscle spasms are poorly understood. According to some authorities, muscle spasms occur because a vicious cycle is created when the initial injury causes muscular pain and spasm, which increases afferent nociceptive input to the spinal cord, further exciting the alpha motor neuron to cause more spasms, and so on.61,96 Other experts believe that muscle spasms occur because of a complex protective mechanism, whereby muscular contractions are intended to support an injured vertebral structure or peripheral joint.96 Regardless of the exact reason, tonic contraction of the affected muscle is often quite painful because of the buildup of pain-mediating metabolites (e.g., lactate). 

Chronic renal failure is associated with long-term exposure to toxins and is mostly related to the secondary pathological changes triggered by the initial injury. These secondary changes are compensatory mechanisms to maintain the function of the whole kidney, but they eventually result in... 

The ulcer may be sterile. Stromal breakdown and progressive ulceration is largely driven by matrix metalloproteinases (MMPs) and serine proteases derived from local comeal cells and from leukocytes sequestered in the cornea in response to the initial injury (Fig. 13.1). Inoculation and replication of pathogenic bacteria at the site of minor epithelial injury releases exotoxins and microbial proteases that potentiate the initial processes of comeal breakdown and amplify endogenous stromal hydrolysis. However, once started, an ulcer can evolve its own biochemical momentum based... 

The respiratory alveolar epithelial response to toxic injury can be rapid, resulting in necrosis and subsequently sloughing of the sensitive type I cells. This type of response is seen with exposure to such toxicants as ozone, nitrogen dioxide, and butylated hydroxy toluene. This injury stimulates the proliferation of the more resistant type II cells. This proliferative response typically peaks at 48h after onset of the initial injury to the type I cells. The increase in number of type II cells can be expected to alter the diffusion capacity of the pulmonary region through populating this membrane with these thicker cells. 

Although inflammatory cytokine profiles differ depending on the skin models used (Ricketts et al., 2000 Sabourin et al., 2002), they were shown to be elevated in response to SM. In contrast, in guinea pig lungs exposed to 2-chIoroethyI ethyl sulfide (CEES) (a mustards analog), the inflammatory cytokine TNF-a was found to be markedly elevated (Das et al., 2003). The inflammatory cytokines exacerbate the effects of CEES (Stone et al., 2003), which would imply that there is an amplification of the initial injury by the mustards. Lipopolysaccharide (LPS), a ubiquitous entity in our environment, also upwardly modulates the damage that CEES inherently causes to cells (Stone et al., 2003). 

The earliest of these developmental abnormalities involve the brain stem. In a unique case, Rodier et al. (1996) reported the nearly complete absence of the superior olive and facial nerve nucleus, with shortening of the brain stem between facial nerve nucleus and the trapezoid body. They concluded that the initiating injury in this autistic brain occurred around the time of neural tube closure, which occurs at about 4 weeks of fetal development (O Rahilly and Muller, 1994). This timing also corresponds to an increased incidence of autism following exposure to the drug thalidomide during pregnancy (Rodier and Hyman, 1998 Miller et al., 2005). 

TBI activates several protein kinase signaling pathways in the hippocampus that are critical for hippocampal-dependent memory formation. In particular, extracellular signal-regulated kinase (ERK), a protein kinase activated during and necessary for hippocampal-dependent learning, is transiently activated after TBI. However, TBI patients experience hippocampal-dependent cognitive deficits that occur for several months to years after the initial injury. Although basal activation levels... 

Murphy and coworkers presented an interesting paper in which they describe an experiment with rabbits that suggests the initial injury to the vessel can be immunologic in nature. In their study, rabbits subjected to allergic injury (horse serum) developed coronary atherosclerosis similar to man while control rabbits, even on a high lipid diet, did not develop... 

Osteoarthritis can occur following a traumatic dislocation, the incidence ranges from 15%-50% and this may be related to the site of the initial injury, the presence of intra-articular loose bodies and the degree of activity following the dislocation. Simple dislocations have a better prognosis than those with an associated fracture (Figs. 13.2,13.3). 

Open reduction is indicated if percutaneous reduction fails, but only if angulation is more than 45°. The results are generally less favourable because of the risks of damage to the delicate blood supply to the radial head and because the initial injury is likely to be worse (Evans 1999b). 

The issues posed to the bum surgeon in the Emergency Room by patients who have suffered extensive and deep bnm injnries are manifold. Modem bum management techniques involve immediate (or very early) excision of all deep bums and this, together with advances in intensive care medicine, means that the initial injury is usually survived. What follows is the tricky bit ... 

Figure 108.2. Schematic representation of events occurring after tissue injury leading ultimately to the perception of pain. The initial injury...

Acute severe injury of the eye with SM might result in recurrent corneal ulcerative disease for the remainder of the patient s life, with a maximum incidence occurring 15-20 years after the initial injury. Based on extensive data, there is a causal relationship between severe exposure to SM and the development of delayed recurrent keratitis. 

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