Characterizing Amylin and Salmon Calcitonin Receptors in Rats

Dunn (2004) gives a good physiological explanation as to how AD presents itself in the body. Starting with a stimulus, a sensory input is carried by undamaged sensory peripheral nerves to the spinal cord. Next the impulses travel up the spinal cord where sympathetic reflexes are stimulated. Upon these nerves being stimulated this causes vasoconstriction in the peripheral arteries. This vasoconstriction causes a sudden increase in blood pressure where the baroreceptors, which are located in the carotids and aortic arch, send the increased blood pressure information to the brain stem. These baroreceptors are triggered due to the increase in blood pressure and try to act as a buffer to the vasoconstriction by dilating the vascular bed above the injury (Krassioukov et al, 2007). The brain stem then tries to decrease the blood pressure by slowing the heart rate. Inhibitory sympathetic messages are attempted to be sent down the spinal cord (Dunn, 2004). These messages will not be successful in decreasing the blood pressure due to the spinal cord injury occurring at or above T6 (Dunn, 2004). Efferent impulses cannot pass through the spinal cord lesion, which in result the peripheral and visceral vessels do not dilate, resulting

which in turn inhibits the second order neurons that transmit the nociceptive signals to the

ERα has been shown to be expressed in dynorphin neurons in the dorsal horn of the spinal cord and directly modulates dynorphin release, which in turn regulates DORs (Gintzler & Liu, 2012). Dynorphin release is often associated with nociception and has been linked to opioid-induced hyperalgesia (Vanderah, Ossipov, Lai, Malan, & Porreca, 2001). Interestingly, dynorphin and KOR activation is also linked to significant analgesia, particularly in women (Gear et al., 1996). Estrogens upregulate KORs in both intact and ovariectomized female rats in a dose-dependent manner (Lawson, Nag, Thompson, & Mokha, 2010). This apparent contradiction can be explained by spinally synthesized estrogen mediating KOR/MOR heterodimerization in the dorsal horn, which switches dynorphin from being pronociceptive to antinociceptive (N. J. Liu, Chakrabarti, Schnell, Wessendorf, & Gintzler, 2011). In areas outside of the spinal cord, mechanisms involving ERα modulating dynorphin release vary by brain location, and also depend on whether or not ERE-dependent pathways are activated (Gottsch et al., 2009).

As mentioned above, opioids are extremely helpful in killing acute and cancer pain. Because opioid receptors are G-protein coupled reactions, the inhibitory G-protein is usually coupled or attached with the receptors (Ghelardini et al., 2015, page 219). The onset of reaction in inhibit the pain is rapid and effective due to multiple inhibitory actions at the terminal site (refer to the previous section of mechanism of action). Besides, the interaction of opioids gradually increases the threshold of pain neuron as well as attenuates the pain subjective evaluation (Ghelardini et al., 2015, page 220).

After perfusion, sciatic nerves and L3, L4, and L5 DRGs ipsilateral to the injury were dissected and removed, and stored overnight at 4 C in 4% paraformaldehyde in 0.1 M phosphate buffer for post-fixation. Nerves were then transferred to a 1X PBS solution, which was changed every 15 days, and stored at 4 C until immunohistochemical processing. To prepare samples for Whole Mount Staining, experimental nerves (right side) and corresponding untreated controls (left side) were washed in PTX (1% Triton

The rodents are given this diet since gestation and received modest fluid percussion when they became 14 weeks old. It was seen that TBI in the rodents caused reduced levels of molecular systems which is important for synaptic plasticity, as well as plasma membrane homeostasis in the lumbar part of the spinal cord.

Although the cause of fibromyalgia is unknown, there are many explanations for what occurs in the nervous system of people afflicted with fibromyalgia. Specific to this are the various reasons for the intense perception of pain. A change to the myofascia surrounding the muscles has been found to be one of the leading causes of pain and other muscular symptoms of fibromyalgia in the majority of cases. Myofascia is the thin, whitish membrane comprised of a material called 'ground substance' that envelopes and protects the muscle like a sack and which is responsible for supporting and connecting all of the body's muscles together[2]. Normally, neurotransmitters pass easily from the interneurons on one side of the myofascia to create action potentials in the motor neurons attached to the muscles. In the case of people with fibromyalgia, however, often the myofascia has lost its elastic properties and hardened. The ground substance within the myofascia, which is usual in a fluid state, has become more like a solid gel. This change in the myofascia hinders or entirely prevents the neurotransmitters from reaching the motor

CSF is produced by arterial blood coming mainly from the choroid plexus at a rate of about 500 ml per day. The clear, colorless fluid bathes the external surfaces its canals and ventricles. CSF protects the brain when jolted. It also keeps the brain buoyant and regulates the chemical environment of the brain. CSF reabsorbed by the arachnoid granules almost as quickly as it is produced, leaving about 150 mL in the body at any given time. CSF is found in the four ventricles of the brain which narrow into the central canal.

This study may provide indirect evidence that could be used in future studies investigating the mechanisms responsible for EIH and clinically as another option for production of analgesia.

the CNS and the bowel by acting at specific saturable opioid receptors in the CNS and other

Molecule X acts specifically on caudal axons as a chemotropic substance that directs them to innervate the rostral tectum.

It is thought that during damage to the spinal cord, high levels of ATP are released that can activate the P2X7 receptor. In pure cultures, P2X7 receptor antagonist are thought to provide protect against the effects of P2X7. This is due to blocking the receptors instead of trying to stop the inflammatory effects. Because the antagonists can selectivly mediate the activation of P2X7, it is the perfect candidate for the therapeutic treatment of spinal cord injurys (Domercq et al., 2009).

Acute Pain is detected by nociceptors which transmit electrical signals through the A-delta and C-fibres to the central nervous system from the pituitary gland (Steeds, 2013). In response to the signals from the hypothalamus, the pituitary gland synthesises beta-endorphins which bind to the mu receptors at the openings of the synaptic nerve terminals (Sprouse-Blum, Smith, Sugai & Parsa, 2010). Morphine is commonly used in the treatment and prevention of sever acute pain. To be an effective pain relief it must be absorbed into the bloodstream. If taken orally, the short lived drug has to make its way through various layers of mucus in the gastrointestinal tract before it eventually

There are two key strategies has emerged out as spinal opioid gene therapy proven to be efficacious to induce analgesia in neuropathic patients. First, several groups have used transgenes encoding endogenous opioid agonists delivered to the DRGs. Goss et al used preproenkephalin, a d-opioid receptor agonist, and endomorphine-2, a μ opioid receptor agonist, delivered by HSV vectors (Goss et al. 2001).

Formalin- prepared optic nerves (ON) was mainly used as the materials and sources of information in the study. To identify the human ON areas where demyelination has occurred, Jennings and Caroll used luxol fast blue (LFB) and hamatoxylin and eosin. Cat ON, on the other hand, were stained with toluidine to distinguish the myelin sheaths in preparation for electron microscopy processing. After this, immunohistochemistry was effectually conducted in order to differentially mark the neuroglia. The digital images formed were then examined and evaluated to quantify the data. Results revealed the presence of oligodendroglial cells in MSON lesions, which further confirms the link between remyelination as a result or consequence of