Mechanisms of Musculoskeletal Pain

Mechanisms of Musculoskeletal Pain Musculo-skeletal pain is a complex sensation where sensory, affective and cognitive dimensions of pain alongwith parallel neural networks in brain are associated with constellation of factors. Though pain occurs to show protective gesture, but when it surpasses threshold, exerts debilitating effect upon health and triggers concomitant physiological and psychological concerns of perilous ramifications. Right from the activation of primary afferent nociceptors upto the cortical processing of the pain in the higher regions of the brain, pain trajectory can be dissected into transduction, conduction, synaptic transmission and modulation. Besides, environmental, behavioral and psychological risks involved, all these stages of pain sensitivity, severity and analgesic responses are mediated by different set of genes and genetic variants. Transduction of noxious stimuli is regulated by transient receptor potential cation channel subfamily M, member 8 (TRPM8) and transient receptor potential cation channel subfamily A, member 1 (TRPA1) encoded by TRPM8 and TRPA1 genes, which plays an important role in the inhibition of background potassium channels. SCN10A encoded, voltage gated sodium channel Nav1.8 is essential for signal generation in response to cold stimuli. The nociception, due to heat stimulus and red hot chili pepper activates the ion channel TRPV1 and capsaicin receptors. However, TRPV1 also regulates the inflammatory pain thresholds, TRPV4, in conjunction with TRPV1 and TRPV2, transduces both thermo and mechano-sensations. The pain related transgenic knockout studies offered significant information on the genes that influence pain transduction. (Lacroix-Fralish ML. etal, 2007). Three genes SCN9A, SCN10A and SCN11A which encode sodium channels are observed to be expressed in sensing neurons. . SCN9A carriers, who have defective Nav1.7 remains pain free, which makes it a novel target for sodium selective analgesic drugs. SCN10A (Nav1.8) is also a significant contributors to the transduction signaling of pain pathway. Though, encoded channel Nav1.8 does not induces action potential but plays a significant role in setting the pain thresholds. SCN11A gets activated, close to the resting membrane potential and mutations in this gene have been associated to the loss of pain perception. Voltage gated sodium channel nociceptors specific genes SCN1A, SCN3A, SCN8A, SCN9A, SCN10A, SCN11A along with potassium channel encoding KCNQ genes play a significant role in nociceptive conduction. Synaptic transmission is regulated by several genes such as GR1N1, GR1N2, GR1A1-4, GR1C1-5, NK1R. Some voltage gated calcium channels encoding genes, such as CACNA1A-S, CACNA2D1 mediates the neurotransmitter release in the pre-synaptic membrane.Several genes and genetic variants have also been implicated in the centr al, peripheral and microglial pain modulation. (Foulks and Wood. 2008). How damage sensing neurons submit input signals regarding the extent and severity of pain to central nervous sytem (CNS) is highly complex. Very many brain areas are involved in sensory discrimination and affective evaluation which determine the nature of pain perception. Genetic variation of COMT gene that encodes catechol-o-methyltransferase regulates the inactivation of catecholamines neurotransmitters and reduced COMT enzymatic activity which leads to increased pain sensitivity and temporal summation of pain (diatchenko L et al. 2005) Decreased adrenalin metabolism due to reduced COMT activity increases pain through the stimulation of ÃŽ ²2/ 3-adrenergic receptor antagonist. A few genome wide association studies (GWAS) on musculo-skeletal phenotypes have been carried out which revealed some strongly associated SNPs within CCT5 and FAM173B genes that influence chronic widespread pain in lumbar spine region. Over the past decade, an intriguing development in cellular genomics has aroused curiosity of the possibility of miRNA in pain research. MicroRNAs (miRNAs) are family of small, noncoding RNAs that regulate gene expression in sequence specific manner. Their non-perfect pairing of 6-8 nucleotides with target mRNA subsequently forming miRNA Induced Silencing Complex (miRISC) generally results in translational repression, destabilization of mRNAs and gene silencing. Some miRNAs have been implicated in pain mechanism including neuronal plasticity, neurogenesis, nociceptor excitability, chronic pain conditions and pain threshold. They engrossed the attention when observed that these miRNAs play an evident role in the conditional deletion in nociceptors of th e miRNA producing enzyme, Dicer and blocks inflammatory pain hypersensitivity. The pioneer studies on the role and relevance of miRNAs in pain demonstrated that miR-134 is modulated in the trigeminal ganglion in response to inflammatory pain. BDNF triggered miR-132 is upregulatedin cortical neurons which is identified as modulation of nociception signaling. miRNA Let-7 that target  µ-opiod receptors plays considerable influence on the opioid tolerance in mice. Activity regulated miR-188 is a significant player of synaptic plasticity tuning. Dysregulation of miR-29a/b is associated with structural plasticity in psycho-stimulant exposure. In the traumatized spinal injury miR-219 is downregulated 7 days after contusion whereby sciatic nerve ligation induces an up-regulation of this miRNA. In chronic pain miR-124 down regulates in dorsal root ganglion neurons in inflammatory muscle as well as in sciatic nerve crush. Researchers are instrumental in understanding the epigenetic mechanisms in relation to pain causation and alleviation. Epigenetic modifications play significant role in cytokine metabolism, neurotransmitter release and response, analgesic sensitivity and central sensitization. Changes in chromatin structure may lead to acute to chronic pin transition. Prior priming (sensitization) of spinal microglia with initial inflammatory challenge, subsequent challenges create enhanced pain intensity and duration. Effects of neonatal pain experience relates to adult pain sensitivity where they exhibit spinal neuronal circuits with increased input and segmental changes in nociceptive primary afferent axons and enhanced or altered pain stimulation. Histone modifications, a significant epigenetic mechanism which may alter the gene expression of pain is highly associated with glutamate decarboxylase (Gad2), Shal related subfamily member 3 (Kcnd3), melting CpG binding protein 2 (Mecp2), potassium vol tage gated channels, oprin 1, Scn9a Genes. Histone acetylation and DNA methylation have also been implicated in chronic pain conditions. Though an epigenetic alteration in relation to the risk of pain is in infancy but in near future, such knowledgeable musings will unravel several novel targets for analgesic drugs and preventive modalities. Brain does more than understanding and responding to pain irrespective of sensory inputs and even in the absence of external inputs. Why even cordectomy or anesthetic blocks of sympathetic ganglia do not stop phantom limb pain? Pain genetics have the capacity to enrich us of several such intricate and unforeseen consequences involved with pain etiology, risk factors and variable analgesia. In future, investigation of relevant genomic sequences has many revelations in store for us, by which we will be able to regulate or control pain by switching on or off various genes that causes it.

Hunger Games Theme

What would we do if we were chosen at random to fight for our life? Would we just let it happen? Would we fight back and try our best to keep out dignity? Or would we do whatever it takes just to stay alive, even if it means losing site of who we really are? These are all decisions that Peeta and Katniss, two kids from a city called Panem had to make all by themselves. The novel The Hunger Games by Suzanne Collins has many themes, but the most important overall, is the importance of keeping dignity and humanity while fighting for our life. In the Hunger Games, a sixteen year old girl named Katniss and a sixteen year old boy named Peeta are chosen to go into the Hunger Games, where they will fight for their lives. During past years, competitors in the Hunger Games would do a number of unspeakable things in order to survive. Peeta however is the complete opposite. He wants to die with dignity. First off, in the novel The Hunger Games, by Suzanne Collins, many things go wrong in Panem, the society that the main characters Katniss and Peeta live in. For example, their society is filled with many things such as war, starvation, poverty, and violence. Peeta and Katnis have been taught since they were little that no matter what you are doing you have to keep your dignity while doing it. Even if it is fighting to the death. The way that both Peeta and Katniss have grown up comes in really handy during the Hunger Games. It makes it extremely easier for them to keep their dignity during the games. However, many competitors will do anything in order to survive, wouldn’t you? Peeta however, is very different; he believes that if he is going to die, he should at least go with his dignity. This means that while everyone else loses their minds, he will still think straight and won’t do anything outrageous in order to survive. For example, a girl from district 9 said â€Å"here’s some advice, just stay alive† (127). This quote shows that she believes the only thing that matters is staying alive. She will risk anything to live, even her humanity and dignity. Peeta however, would basically rather die with his dignity than live knowing he completely lost his dignity and humanity during the Hunger Games. To Peeta, his dignity is just as important as his own life. The competitors in the Hunger Games family and friends are also loosing spite of their humanity and dignity even though it may not seem like it to them. The family members show their loss of dignity when all of them just sit back and watch as their loved ones battle for their lives. It is just one big game to them. Celebrations are thrown if their loved one kills another person’s loved one. They don’t even comfort the other family at all. Everyone just parties while one family is having one of the worst possible days of their lives. Watching as somebody’s child is being killed isn’t right. Imagine if our society was like this. We wouldn’t just sit back and watch as our family and friends die before our eyes, would we? The novel The Hunger Games is similar to the novel Lord of the Flies by William Golding in a few ways. The most important however is the characters loss of humanity and dignity, which occurs in both novels. In Lord of the Flies, the large groups of boys that are stranded on the island lose sight of what is really important to them. They get caught up in trying to stay alive and doing whatever it takes to stay alive. Jack, from Lord of the Flies, ran around chanting â€Å"Kill the pig. Cut her throat. Spill her blood† (69). This quote shows us that the boys are starting to lose their dignity. This is exactly what happens in Suzanne Collins, Hunger Games. All of the competitors chosen to compete in the annual Hunger Games get caught up in killing people to stay alive that they forget who they really are inside. Ralph, the boy from the novel Lord of the Flies is very similar to Peeta, the boy from the novel Hunger Games in many ways. For example, both Ralph and Peeta are one of the only people to keep their humanity and dignity while they are stranded on an island or in this case fighting to the death in a huge arena. All of the boys in the novel Lord of the Flies lose their dignity and humanity except for Ralph and piggy who stay sane. This is very similar to the Hunger Games. Everyone in districts one through eleven go crazy and forget who they are except for two people. Only Peeta and katniss who are from District 12 keep their dignity while struggling to stay alive. Peeta says â€Å"at least let me die with my dignity† (167). This quote shows us that Peeta won’t lose his humanity and dignity no matter what. In conclusion, the novel The Hunger Games by Suzanne Collins shows us how society could end up if we lose sight of our dignity. She shows us that just because something bad could happen doesn’t mean that we have to forget what really matters to us, or even forget who we truly are behind all of the violent, or just plain old fake acts that we would have to put on just to live through the Hunger Games. She shows us through the eyes of Peeta that even when something gets tough, we just have to work through it and keep our head held high.

Human Services Leadership Essay - 963 Words

Select an area of human services in which you currently work, or would like to work. ï‚ · Write a 700- to 1,050-word paper addressing why ethics and ethical leadership is important in that field. a. Discuss the moral responsibilities you would have as a leader in your field of focus. b. Develop a moral vision or road map that would guide you as a human service leader. c. Incorporate your personal values and the particular ethics of your chosen field into that moral vision. d. Think about your guiding principles, plans for the future, and what you hope to achieve as a leader when creating your moral vision. The main duty of the social work profession is to improve human welfare and to†¦show more content†¦(Wikipedia, 2010). Leadership, a critical management skill, is the ability to motivate a group of people toward a common goal. Leadership is about vision, principle and integrity. Self would define it as a power to motivate others through your words and deeds. And Ethical leadership is ethically motivating others in ethical directions. Its knowing your core values and having the courage to live them in service of the common good. Human Services is a very sensitive field where ethics are of great importance. We would expect to find issues associated with ethical decisions in Human Services. Taking it seriously is to treat people influenced by their decision with the dignity and respect they are due. Best results can be produced because a broad range of inputs has been considered. Humans are most important and treating them with respect and dignity is the essence of Human Servic es. Knowledge and Courage are the two most important ingredients of Ethical leadership. Another important pillar of this building is the imagination. Lack of imagination stops you from looking beyond the usual confines of an issue. The ultimate goal of a leader is always recognition and fame but of an ethical leader is the Respect in the hearts of the people. 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Leadership Reflection - 944 Words

Ronetta Lewis HSA 4939 Leadership Reflection Report Leadership is the root of change, whether it be in a person, organization, or both. It is a skill that is best to be built upon during one’s entire life and it’s capable of affecting a vast number of people. Everyone automatically assumes that people in higher positions are leaders when in all actuality, anyone has what it takes to be a leader. There are principles of leadership well beyond the book we were assigned to read, but I’m grateful to have gotten to learn about (and apply) a few of them to the outpatient clinic. Without knowing about the principles to be discussed in the following paragraphs, I most likely would not have displayed the leadership skills that I have during my†¦show more content†¦As a new practice manager, this caused me to step out of my comfort zone and quickly devise a plan to get the clinic back on track. After noting the issues, I talked it over with my subordinates, and advised that we worked to gether to achieve the best results. I provided insight (stage two) to them on how we could improve patient satisfaction, avoid HIPAA violations by not leaving medical records exposed, and stressed the importance of communication. I also informed them about the importance of their roles and that being absent without a heads up, sets everyone back. In the way that I delivered the message without demeaning anyone, this led to the third stage of ‘will = intentions + actions’. Since everyone now had direction and proper guidance, all that was left for us to do was commit to our individual tasks. In no time, the clinic was back in good standings and we were all getting along well, resulting in a positive atmosphere that was noticeable to our outpatients. This principle led to a domino effect, whether it was positive or negative depended on us. 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