Pain: Causes, Concerns and Consequences

Pain is a percept: it is an unpleasant sensory and emotional experience, a product of the brain’s abstraction that might be considered an activity mediated event: the activity being the message and pain the messenger warning of imminent or actual injury or imbalance yet to be avoided or resolved. There are no ‘painful stimuli’ that is stimuli that invariably elicit the perception of pain in all individuals and it is this highly individual and subjective nature of pain that makes it difficult to define and to treat clinically. The key to understanding and therefore appropriate treatment is in deciphering the message. Recognising and respecting the interdependence of both the clinician and researcher in the search for deeper discernment proffers the potential for synergistic evolution in understanding and treatment with the promise of bringing relief to many sufferers of both explained and unexplained pain.

Central post-stroke pain (CPSP) results from lesions or dysfunction of the spinothalamocortical pathway. Pathophysiological mechanism of CPSP may include contralateral somatosensory cortex or bilateral mid- and posterior insula, anterior insula, posterior cingulate cortex and spinothalamocortical pathway. Our [14C] iodoantipyrine data from animal model of CPSP indicated that significantly higher activation occurs in the medial prefrontal cortex (mPFC), anterior cingulate cortex, thalamus, hypothalamus, amygdala and periaqueductal gray (PAG). We propose a neural correlation hypothesis of CPSP, in which the mPFC-amygdala pathway, hypothalamus and PAG interact with each other and the spinothalamocortical pathway, resulting in the manifestation of CPSP symptoms. These symptoms can include depression, anxiety, motor disturbances and cognitive dysfunction in thalamic stroke patients, in addition to CPSP. Alterations in different brain activation and circuitry connections in CPSP may help in understanding the pathophysiological mechanisms underlying multiple aspects of CPSP symptoms. Such novel ideas may be applied to develop pharmacological and non-pharmacological interventions for CPSP.

Chest pain as a common symptom in general population is considered to be the second most common cause of presentation to emergency departments of medical centers. Such pains are categorized broadly into cardiac chest pain (CCP) vs. noncardiac chest pain (NCCP). In patients with cardiac diseases, the main symptoms of psychological reactions to pain include psychological stress, fear and anxiety, pain resulting from anxiety, and anxiety and depression as a result of pain. Furthermore, there is a relationship between perceived psychological factors and the psychological distress, and sustained NCCP could lead to the development of depression, stress and low mental quality of life. Controlled clinical trials on treating CCP and NCCP have shown that these relatively extensive interventions have been effective in reducing psychological distress, periods of chest pain frequency, and lowering functional problems.

Pain is the most prevalent form of human health malady which, if remain unaddressed, exerts formidable impact. Pain research has tried hard to unravel the possibilities in the direction of diagnosis and management of pain conditions, but knowledge of genetic consequences of pain is still in infancy. During pain, sensory input is realized, processed and regulated, first and foremost through ones genetic composition and then different characters of physiology, psychology, sociology and environment come in the scene. The present exposition demonstrates the precise details of various genes and genetic variants that participate in different phases of pain and pain conditions, disseminating an idea that in future, diagnosis and treatment of pain by harnessing indepth genetic knowledge has startling revelations in store for us.

Chronic non-cancer pain (CNCP) presents significant challenges to physicians and when combined with co-occurring diseases such as substance use disorder (SUD) the challenge becomes magnified. It is important that the physician realizes that both CNCP and SUD are diseases of the brain, mind, body, and spirit and, therefore, consideration of the whole person and their life experience is essential. In formulating a treatment plan, the physician should remember the cognitive and emotional changes that have occurred as a result of the disease’s effect upon the and mind. The proper treatment of the patient should also include treatment of chronic stress and its consequences. The physician should be aware of the alternative modalities such as mind-body, psychosocial, and technology based treatments. Many are available to the patient locally and can also be accessed through the internet. Physicians who treat complex CNCP patients should begin to implement these modalities in a comprehensive treatment plan that restores balance to the patient with CNCP and SUD and allows the patient to become an active participant in their care.

Pain is a debilitating condition which is the leading cause of cognitive, mood and anxiety disorders. It is one of the major medical burdens on human health which obstructs the quality life of a person as the appropriate therapeutic solution is not available. Due to advancement of new genomic technologies, it is now possible to view genome wide changes during chronic pain in different cell types from the somatosensory system to the neurons in central nervous system. Tremendous research over recent years has enlightened the magical potential of small non-coding RNAs, mainly microRNAs in modulating numerous pathophysiological processes including proliferation, apoptosis and oncogenesis. They target a wide range of molecules and refine their protein output and thus, fine tune distinct cellular processes including pain signaling. Recently, animal models depicting inflammatory and neuropathic pain and patient subjects complaining distress due to pain have shown deregulations of miRNAs in affected tissues and systemic circulation. Although various painful conditions viz. spinal cord injury, peripheral nerve injury, cancer and inflammatory diseases have been recognized with genome-wide changes in microRNA signatures, yet the gene regulatory networks underlying pathological significance of individual microRNAs are sparsely studied. Hence, this chapter summarizes the latest findings addressing the role of microRNAs in various inflammatory or neuropathic pain conditions. How can miRNA research be expedited in revealing new aspects of pain pathophysiology is also addressed. The chapter also uncovers the novel potentials of miRNAs as well as roadblocks in the path of miRNA based anti-nociceptive therapies.

The present study was designed to investigate the analgesic potential of 7- hydroxy-4-methylcoumarin (HMC) in acrylamide induced neuropathic pain in rats. Acrylamide (30 mg/kg, i.p.; once in three days, for 24 consecutive days) was administered for inducing neuropathic pain. The acrylamide induced nociceptive pain sensation, i.e., acetone drop, plantar, hot plate, Von Frey Hair and tail immersion tests have been assessed at different time intervals, i.e., 0, 6, 12, 18 and 24th day. Furthermore, the biochemical estimation, i.e., thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH), total calcium, cytochrome c oxidase activity and ATP content levels were estimated from the sciatic nerve tissue sample on 24th day. The HMC (10 and 20 mg/kg, p.o.) and cyclosporin A (CsA, 50 μM/kg; p.o.) was administered for 24 consecutive days, one hour before each injection of acrylamide. The treatment of acrylamide resulted in significant (P < 0.05) changes of behavioral and biochemical changes. Pretreatment of HMC ameliorate the acrylamide induced changes of behavioral and biochemical parameters in a dose dependent manner. These results are similar to that of CsA treated group. Based on these findings, it may conclude that, HMC possesses the potential ameliorative effect against acrylamide induced neuropathic pain, it may be because of its therapeutic potential of anti-oxidant, anti-lipidperoxidative, calcium ion regulatory and mitochondrial permeability transition pore inhibitory action.