The inflammatory mediators activate local pain receptors and nerve terminals and produce hypersensitivity in the area of injury. Activity of the mediators results in excitation of pain receptors in the skin, ligaments, muscle, nerves and joints. Excitation of these pain receptors stimulate the specialized nerves e.g. C fibers and A-delta fibers that carry pain impulses to the spinal cord and brain. Subsequent to tissue injury, the expression of sodium channels in nerve fibers is altered significantly thus leading to abnormal excitability in the sensory neurons. Nerve impulses arriving in the spinal cord stimulate the release of inflammatory protein Substance P. The presence of Substance P and other inflammatory proteins such as calcitonin gene-related peptide (CGRP) neurokinin A and vasoactive intestinal peptide removes magnesium induced inhibition and enables excitatory Inflammatory proteins such as glutamate and aspartate to activate specialized spinal cord NMDA receptors. This results in magnification of all nerve traffic and pain stimuli that arrive in the spinal cord from the periphery. Activation of motor nerves that travel from the spinal cord to the muscles results in excessive muscle tension. More inflammatory mediators are released which then excite additional pain receptors in muscles, tendons and joints generating more nerve traffic and increased muscle spasm. Persistent abnormal spinal reflex transmission due to local injury or even inappropriate postural habits may then result in a vicious circle between muscle hypertension and pain [7] [5]. Separately, constant C-fiber nerve stimulation to transmission pathways in the spinal cord results in even more release of inflammatory mediators but this time within the spinal cord. Inflammation causes increased production of the enzyme cyclooxygenase-2 (Cox-2) and 5-lipoxygenase (5-LOX), leading to the release of chemical mediators both in the area of injury and in the spinal cord. Lipoxygenases (LOX) and cyclooxygenase (COX) enzymes can insert oxygen into the molecule of arachidonic acid and thereby synthesize inflammatory mediators leukotrienes [due to 5-lipoxygenase (5-LOX) activity] and prostaglandins (via COX activity) [8] . Widespread induction of Cox-2 expression in spinal cord neurons and in other regions of the central nervous system elevates inflammatory mediator prostaglandin E2 (PGE2) levels in the cerebrospinal fluid. The major inducer of central Cox-2 upregulation is inflammatory mediator interleukin-1 in the CNS [9] [6]. Basal levels of the enzyme phospholipase A2 activity in the CNS do not change with peripheral inflammation.. Abnormal development of sensory-sympathetic connections follows nerve injury, and contributes to the hyperalgesia (abnormally severe pain) and allodynia (pain due to normally innocuous stimuli). These abnormal connections between sympathetic and sensory neurons arise in part due to sprouting of sympathetic axons. Studies have shown that sympathetic axons invade spinal cord dorsal root ganglia (DRG) following nerve injury, and activity in the resulting pericellular axonal ‘baskets’ may underlie painful sympathetic-sensory coupling [10] . Sympathetic sprouting into the DRG may be stimulated by neurotrophins such as nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin‑3 (NT‑3) and neurotrophin 4/5 (NT‑4/5). The central nervous system response to pain can keep increasing even though the painful stimulus from the injured tissue remains steady. This “wind-up” phenomenon in deep dorsal neurons can dramatically increase the injured person’s sensitivity to the pain. Local tissue inflammation can also result in pain hypersensitivity in neighboring uninjured tissue (secondary hyperalgesia) by spread and diffusion of the excess inflammatory mediators that have been produced as well as by an increase in nerve excitability in the spinal cord (central sensitization). This can result in a syndrome comprising diffuse muscle pain and spasm, joint pain, fever, lethargy and anorexia.