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Itch & Pain
Number of Followers: 2  

  This is an Open Access Journal Open Access journal
ISSN (Online) 2377-9756
Published by Smart Science and Technology LLC Homepage  [19 journals]
  • Toll-like receptor 2 signaling induces interferon regulatory factor 8
           expression in spinal cord microglia after peripheral nerve injury

    • Authors: Hyoungsub Lim, Minsu Gwon, Sung Joong Lee
      Abstract: Although it is well known that spinal cord microglia activation plays a causal role in the development of neuropathic pain after peripheral nerve injury (PNI), the mechanisms of this activation have not been completely elucidated. We have previously shown that toll-like receptor 2 (TLR2) is involved in PNI-induced spinal cord microglia activation. A more recent study showed that PNI induces interferon regulatory factor 8 (IRF8), which is a key transcription factor responsible for microglia activation. In this study, we investigated the putative role of TLR2 in IRF8 expression in spinal cord microglia after PNI. In TLR2 knockout mice, nerve injury-induced spinal cord IRF8 expression was severely compromised. In addition, an intrathecal injection of lipoteichoic acid (LTA), a TLR2 agonist, induced IRF8 mRNA expression in the spinal cord. Lastly, TLR2 stimulation by LTA induced IRF8 mRNA expression in primary spinal cord glial cells. TLR2-induced IRF8 expression was dependent on p38 MAPK and NF-κB activation. Taken together, these data show that TLR2 activation induces IRF8 expression in spinal cord microglia after PNI.
      PubDate: 2017-01-02
      DOI: 10.14800/ip.1457
      Issue No: Vol. 3 (2017)
  • Successful treatment of persistent visual aura with lamotrigine

    • Authors: Hannah L. Kirsch, Kasra Maasumi
      PubDate: 2016-11-28
      DOI: 10.14800/ip.1458
      Issue No: Vol. 3 (2016)
  • Neuromediators for cholestatic pruritus

    • Authors: Hongzhen Hu
      Abstract: Cholestatic pruritus is one of the most common complaints in patients with liver diseases and intra- or post- hepatic cholestasis. The mechanisms of cholestatic pruritus remain poorly understood although multiple factors are considered to participate in the pathogenesis of cholestatic pruritus. Recent exciting studies have discovered several G-protein coupled receptors (GPCRs) and endogenous chemical ligands that play critical roles in mediating cholestatic pruritus in animal models and patients. These new findings have provided novel insights into the molecular and cellular mechanisms of cholestatic pruritus and improved our understanding of the etiology and treatment for the condition.
      PubDate: 2016-11-14
      DOI: 10.14800/ip.1451
      Issue No: Vol. 3 (2016)

    • Authors: Xian-Min Yu, Xing-Hong Jiang
      Abstract: Neurons in the trigeminal subnucleus caudalis (Vc) and spinal cord dorsal horn (SDH) play important roles in modulating and relaying pain signals to the higher centers of the central nervous system (CNS). Morphologically, many aspects including a laminated structure, cytoarchitecture and cellular elements in these two central regions are very similar [1,2,3,4]. Most nociceptive afferents with a small-diameter terminate in the superficial laminae of Vc and SDH. Functionally, sensory neurons in Vc and SDH respectively receive nociceptive inputs from the orofacial and other somatic regions, and convey the inputs to higher brain centers [1,2,3,4,5]. According to the mechanoreceptive properties, sensory neurons in both the Vc and SDH are classified into three types. They are low-threshold mechanoreceptive (LTM), wide-dynamic range (WDR) and nociceptive-specific neurons (NS) [1,2,3,4,5]. Because of these similarities Vc has been considered as analogous to SDH [4,6]. However, some differences between Vc and SDH have also been reported. For example, the distribution pattern of substance P (SP) and calcitonin gene related peptide (CGRP) in Vc of adult animals is different from that in SDH. In SDH there is no dual representation of peripheral regions, which can be found in rostral and caudal Vc. A transitional zone found between Vc and trigeminal subnucleus interpolaris plays a special role in sensorimotor function. However, no such region is found in the spinal system [5,7,8]. CNS neurons are regionalized. They are organized as groups through their circuitry. Although it is known that differences in functions among these groups in the adult CNS are predetermined during the development of the neuroepithelium [9,10,11,12,13], understanding how the regional specificity is developed in the CNS is still a big challenge in neuroscience research. It has recently been found that ninhydrin-reacting small molecules released locally are involved in the region-specific regulation of neuronal development in cultured Vc and SDH neurons [14,15]. In this review we focused on present knowledge about the region-specific regulation of neuronal development in these two CNS regions associated with the transmission of nociceptive signals.
      PubDate: 2016-06-13
      DOI: 10.14800/ip.1341
      Issue No: Vol. 3 (2016)
  • Research Highlights: Pain Control in Orthodontics Using Vibration

    • Authors: Wendy D. Lobre, William J. Dunn
      Abstract: Pain is a common patient complaint during the orthodontic movement of teeth, especially immediately following archwire placement.  Vibration has been used to accelerate the orthodontic movement of teeth and some observations by clinicians have indicated that vibration appeared to reduce the pain of orthodontic treatment.  The purpose of this parallel group, randomized clinical trial was to investigate the relationship between a micro pulse vibration device and pain perception during orthodontic treatment.  Fifty-eight patients meeting eligibility criteria were assigned using block allocation to one of two groups:  an experimental group using the vibration device or the control group (n = 29 for each group).  Patients used the device twenty minutes daily.  Patients rated pain intensity on a visual analog scale at appropriate intervals during the weeks after the separator or archwire appointment. Data were analyzed using repeated measures analysis of variance at α = .05.  Over the four month test period significant differences between the micro pulse vibration device group and the control group for overall pain (P =.002) and biting pain (P=.003) were identified.  The authors observed that perceived pain was highest at the beginning of the month, following archwire adjustment.  The micro pulse vibration device significantly lowered the pain scores for overall pain and biting pain over the four month study period. 
      PubDate: 2016-02-01
      DOI: 10.14800/ip.1165
      Issue No: Vol. 3 (2016)
  • Prostaglandin D2 improves IL-31-induced alloknesis: itch-stimulation
           becomes pain-stimulation in mouse skin

    • Authors: Iwao Arai, Minoru Tsuji, Kazuya Miyagawa, Hiroshi Takeda, Nobutake Akiyama, Saburo Saito
      Abstract: We examined the effect of prostaglandin D2 (PGD2) on IL-31-induced alloknesis in mice. We investigated itch-associated scratching behavior (long-lasting scratching: LLS) as an indicator of itching. Topically applied PGD2 and dexamethasone each significantly suppressed IL-31 (acute or repeated administration)-induced LLS.  However, neither PGD2 nor dexamethasone suppressed the IL-31 (repeated administration)-induced increase in IL-31 receptor A mRNA expression in dorsal root ganglia. Next, we investigated the scratching behavior induced by pruritogens (histamine, serotonin and compound 48/80) or algogens (acetylcholine, bradykinin and capsaicin) in IL-31-induced itchy-skin mice. In naïve mice, these irritants caused many counts of short-lasting scratching (SLS) and a few counts of LLS for 60 min. In contrast, IL-31-induced itchy-skin mice showed significant increases in LLS counts compared with naïve mice. Topical application of PGD2 significantly suppressed LLS counts induced by these pruritogens or algogens in IL-31-induced itchy-skin mice. The anti-pruritic efficacy of PGD2 may be related to its ability to reverse the hyperkinesis of primary afferents; thus, PGD2 improves IL-31-induced alloknesis. In a hot-plate test, topical application of PGs (PGD2, PGE2 and PGI2) caused a decrease in the nociceptive threshold in naïve mice, indicating that PGs enhance pain. These results suggest that PGs (especially PGD2) can change itch-stimulation into pain-stimulation in itchy-skin mice caused by pretreatment with IL-31. Therefore, it is possible that IL-31 and PGs may play a role in the regulation of a primary sensory nerves for the sensation of itch and pain.
      PubDate: 2016-01-12
      DOI: 10.14800/ip.1138
      Issue No: Vol. 3 (2016)

    • Authors: Arzu Yagiz On
      Abstract: The question whether Fibromyalgia syndrome (FMS) is a distinct clinical entity in the context of chronic widespread pain (CWP) have remained challenging after decades of research and several diagnostic criteria that have attempted to clarify FMS. A recent study has raised more challenges on the issue, proposing that diagnosis of FMS in patients representing with CWP is not informative or helpful for clinical practice and such a differentiation will provide little or no significance regarding the choice of effective and safe therapies. This proposal will be further discussed here by reviewing the recent advances in the field of pain medicine. These advances have collectively provided compelling evidence that all individuals with chronic pain, even those classically categorized as originating from peripheral/nociceptive origins have common central contributions to their pain and associated comorbidities. The recent understanding of the pain mechanisms has also provided important implications on classification and management of pain. Centrally acting agents have been recommended as first-line treatment options for FMS and potential use of these agents has been expanded to other chronic pain disorders. After having reviewed the recent advances in the pain field, distinction between CWP and FMS still seems not to be useful in clinical practice, as effective treatment in an individual patient might be much guided by dominant underlying mechanisms rather than specific diagnosis the patient is suffering. The conditions representing with CWP in the absence of definitive objective confirmation may then be classified under one heading such as “CWP”, “chronic pain syndrome” or “central pain”, when considering their similar pattern of clinical presentation, commonality of central sensitization to their pathophysiology and their similar response to centrally acting analgesics.  Future research should be directed toward classification of CWP based on the validated measurements of different aspects of pain.  Such a classification may help clinicians identify the patients who will preferentially respond to peripheral or centrally acting analgesics and may therefore assist in advancing a more individualized and pain mechanism focused treatment in the clinical setting. 
      PubDate: 2016-01-04
      DOI: 10.14800/ip.1079
      Issue No: Vol. 3 (2016)
  • A Review of Techniques used for Evaluating Lower Urinary Tract Symptoms
           and the Level of Quality of Life in Patients with Chronic Pelvic Pain

    • Authors: Jorgen Quaghebeur
      Abstract: Although the prevalence of CPPS is somewhat uncertain, the cost to society in order to manage it is huge. CPPS presents itself with a variety of symptoms attaining multiple systems. The symptoms and discomfort have been evaluated using questionnaires (e.g. MPQ-DLV, PDI, NIH-CPSI, ICSI, and PUF). Very different results have been found. This indicates that results from one questionnaire cannot be used for overall conclusions concerning pain intensity and QoL, although for bladder symptoms the results seem more corresponding. No gender difference has been found in questionnaire based symptom scores. Women with CPPS are less sexually active and have a higher impact on the QoL compared to men.The result of treatment, will greatly depend on an accurate diagnosis. A thorough clinical assessment using a ‘four step plan’ with special attention to the musculoskeletal system is very valuable The physical examination including palpation and neurodynamic assessment can help indicate pain points and peripheral neuropathies.Constant current perception threshold (CPTs) in healthy volunteers showed that for all measures the female CPTs were lower than these of men. But determining normative CPTs proved problematic: A weak intraclass correlation has been shown with one week interval. Both for the pudendal and the median nerves deviating values in healthy volunteers using sinusoidal stimulation have been found. Our normative CPTs showed almost no agreement with control groups in other studies. The search for a reliable and reproducible semi-objective evaluation of sensory function in CPPS patients must be continued.
      PubDate: 2015-03-16
      DOI: 10.14800/ip.659
      Issue No: Vol. 3 (2015)
  • Molecular Mechanisms of Itch and Pain: An Overview

    • Authors: Sung Joong Lee
      Abstract: Itch and pain are two distinct sensory modalities elicited by noxious and pruritic stimuli, respectively. The cellular and electrophysiological characteristics of itch and pain are very similar; thus discerning the mechanical difference between these two sensory modalities has long been elusive. Recent advances in this field have revealed various neuronal receptors responsible for itch and pain signal transduction and transmission. These studies have identified a distinct sub-population of sensory neurons that are dedicated to the itch sensation. In addition, itch and pain information conveyed to the spinal cord are processed and regulated by distinct spinal cord neurons. Although both itch and pain senses are required for our daily lives, chronic and hyper-sensation of itch and pain results in a debilitating disease state. Studies have now begun to elucidate mechanisms for the peripheral and central sensitization of pain and itch and also to unravel counter-regulatory mechanisms between itch and pain at the spinal cord level. Interestingly, toll-like receptors (TLRs), an innate immune receptor, has been implicated in the central sensitization of both pain and itch. In this review, we will briefly provide an overview of the molecular mechanisms of itch and pain. Additionally, we will discuss the recently uncovered role of TLRs in itch and pain sensation.
      PubDate: 2015-01-28
      DOI: 10.14800/ip.554
      Issue No: Vol. 3 (2015)
  • Features of migraine aura as "Holy Grail" for studying pathophysiology of
           migraine with aura

    • Authors: Igor Petrusic, Jasna Jancic, Jasna Zidverc-Trajkovic
      First page: 10
      Abstract: A first experience of complex migraine aura symptoms can be challenging for physicians to diagnose on a basis of patients report. Also, great variety and abundance of symptoms during migraine aura represent a great model for investigation of brain networks and pathophysiology of higher cortical functions. Moreover, knowledge about the pathophysiology of the migraine with aura is still not entirely understood. We strongly believe that clinical descriptions accompanied with contemporary neuroimaging continuous to play an important role in investigations of the migraine aura. Herewith, we will try to highlight findings in our previous studies with the addition of a reference to allodynia in migraineurs. First experience of complex migraine aura symptoms can be challenging for physicians to diagnose on a basis of patients report. Also, great variety and abundance of symptoms during migraine aura represent a great model for investigation of brain networks and pathophysiology of higher cortical functions. Moreover, knowledge about pathophysiology of the migraine with aura is still not entirely understood. We strongly believe that clinical descriptions accompanied with contemporary neuroimaging continuous to play an important role in investigations of the migraine aura. Herewith, we will try to highlight findings in our previous studies with the addition of reference to allodynia in migraineurs.
      PubDate: 2015-09-02
      DOI: 10.14800/ip.974
      Issue No: Vol. 2, No. 2 (2015)
  • Why is core spine integrity related to low back pain'

    • Authors: Paul S. Sung
      First page: 10
      Abstract: Low back pain (LBP) is the most commonly encountered medical condition in health care. There is growing scientific evidence supporting exercise programs as an effective means of achieving lasting relief from pain. However, understanding the mechanism of spinal integrity with a sensitive measurement is still lacking. There were two purposes of the research highlights: (1) To compare the effects of stabilization and flexibility intervention for subjects with LBP with a combined approach of spinal integrity exercise (SIE) and (2) To measure spinal integrity and outcome assessment by kinetic and kinematic assessment with a core spine model for postural adaptation.The current outcome assessment for the stabilization and flexibility intervention was reviewed based on the disability/pain level, quantification of balance sway, muscle response time in the sudden load environment, and fatigability of trunk muscles from electromyography (EMG). The level of pain and disability did not demonstrate convincing evidence of treatment differences, although the flexibility group demonstrated better scores. For balance sway, there was a significant treatment, hand dominance, trial, and time interaction in the anterior/posterior plane. For the muscle response time, there was a significant hand dominance, muscle group, assessed side, and time interaction. The hand dominance contributed significantly greater fatigue on their non-dominant side of the erector spinae muscles. However, these results needed to clarify interactions on musculoskeletal changes with neuromuscular adaptation in subjects with LBP. Exercise interventions that consider the kinetic and kinematic indices may enhance these interactions, quality of care, measurement of spinal function, and modify specific rehabilitation strategies.The combined kinetic and kinematic indices analyzed proprioceptive responses with visual input and core spinal control during one leg standing. The core spine model was also used to compare motor control and sensory feedback for the ability to refine postural adaptations as indicated by diminished motor control in the LBP group. Furthermore, these combined indices could be utilized to gain a better understanding of new concepts of compensation for integrated balance performance in order to enhance evidence-based rehabilitation strategies. Clinician need to apply these indices for optimal injury prevention by core spine training and pain control in subjects with LBP.o:lock v:ext="edit" aspectratio="t"/> Paul Sung
      PubDate: 2015-08-25
      DOI: 10.14800/ip.932
      Issue No: Vol. 2, No. 2 (2015)
  • Interleukin-31 (L-31) causes alloknesis: pain-stimulation becomes
           itch-stimulation in mouse skin

    • Authors: Iwao Arai, Minoru Tsuji, Kazuya Miyagawa, Hiroshi Takeda, Nobutake Akiyama, Saburo Saito
      First page: 10
      Abstract: We investigated the effect of itchy skin on irritant-induced scratching behavior in relation to itch or pain expression in mice. Itchy skin was caused by either mite-infestation or the intravenous injection of IL-31. Scratching behavior was detected automatically and evaluated objectively using a personal computer. Two kinds of scratching behavior are observed in mice: long-lasting scratching (LLS) and short-lasting scratching (SLS).  LLS (scratching duration over 1.5 s) is frequently seen in spontaneous skin-lesioned NC/Nga mice, but not in other strains of non-skin-lesioned mice. We investigated LLS as an indicator of itching induced by histamine, serotonin, compound 48/80, acetylcholine, bradykinin or capsaicin in mite-infested or IL-31-pretreated mice. These irritants caused many counts of SLS and a few counts of LLS for 60 min. Itchy-skin mice showed significant increases in LLS counts compared with a control group.  These mice showed sustained scratching behavior, which serves as a measure of the itchy sensation, in response to not only pruritogens such as histamine, serotonin and compound 48/80, but also to algogens such as acetylcholine, bradykinin and capsaicin. These data suggest that pretreatment with IL-31 changes non-selective irritant stimulation into itch-stimulation in mice.  The itchy skin in these mice closely resembled the “alloknesis” or “hyperknesis” observed in atopic dermatitis patients. Pain and itch are transmitted through the same nerve fibers, a sensation is perceived as pain or itch depending on the operation of IL-31.
      PubDate: 2015-08-03
      DOI: 10.14800/ip.924
      Issue No: Vol. 2, No. 2 (2015)
  • Myositis as a Presenting Manifestation of Severe Hypothyroidism: A Case
           Report and Review of the Literature.

    • Authors: Amir Emamifar, Rikke Andreasen Asmussen, Klaus Levin, Inger Marie Jensen Hansen
      First page: 10
      PubDate: 2015-05-31
      DOI: 10.14800/ip.845
      Issue No: Vol. 2, No. 2 (2015)
  • : Severe Joint Pain as a Manifestation of Paraneoplastic Rheumatic
           Syndrome in a Patient with a Malignant Lymphoma: A Case Report and Review
           of the Literature

    • Authors: Rikke Asmussen Andreasen, Amir Emamifar, Jacob Christian Bang, Michael Boe Møller, Inger Marie Jensen Hansen
      First page: 10
      PubDate: 2015-04-13
      DOI: 10.14800/ip.759
      Issue No: Vol. 2, No. 2 (2015)
  • Is Acid Painful or not'

    • Authors: Sitt Wai Fong, Wei-Nan Chen, Chih-Cheng Chen
      First page: 10
      Abstract: Acid (or proton) is an effective algogen to excite primary afferent nociceptors and evoke pain. Pain associated with tissue acidosis occurs where there is/are tissue injury, inflammation, ischemia, fatiguing exercise, or tumors. However, a recent study in mice has virtually changed our view regarding the significance of acid signaling in nociception. In the study, an acid-induced muscle pain model was used to probe the endogenous antinociceptive signaling pathway. Surprisingly, instead of acid-induced pain, the authors discovered that acid could also elicit an antinociceptive effect on mice, when specific acid sensors of muscle nociceptors, such as ASIC3 and TRPV1, were blocked. The acid-mediated antinociceptive pathway might act via a subset of acid-sensitive muscle afferent neurons to release substance P (SP), which would act on neurokinin 1 (NK1) receptors to reduce acid-induced depolarization via activation of an M-type potassium channel. The newly uncovered antinociceptive role for acid has largely changed our concept of pain biology and brought new insight for the analgesic drug development.
      PubDate: 2015-04-07
      DOI: 10.14800/ip.721
      Issue No: Vol. 2, No. 2 (2015)
  • Increased itching sensation depends on an increase in the dorsal root
           ganglia IL-31 receptor A (IL-31RA) expression in mice with atopic-like

    • Authors: Iwao Arai, Minoru Tsuji, Kazuya Miyagawa, Hiroshi Takeda, Nobutake Akiyama, Saburo Saito
      Abstract: While itching and scratching are important factors in the development of atopic dermatitis (AD), the mechanisms that underlie these phenomena are poorly understood. Cohousing with skin-lesioned NC/Nga mice, an animal model of AD, gradually increased itch-associated scratching behavior (LLS) counts in several strains mice. On the other hands, repeated dose of interleukin-31 (IL-31) gradually increased LLS counts due to increasing of dorsal root ganglia (DRG) IL-31 receptor A (IL-31RA) expression in mice.We investigated the relationship between the LLS counts and the expression of IL-31 and IL-31RA mRNA in the skin and DRG in mice. The LLS counts were significantly increased in NC/Nga and BALB/c mice after 3, 7 and 14 days cohoused with skin-lesioned NC/Nga mice, in a duration-dependent manner. Cohousing with skin-lesioned NC/Nga mice significantly increased the expression of mRNA for cutaneous IL-31 and DRG IL-31RA compared with these levels in non-cohoused NC/Nga and BALB/c mice, while DRG IL-31 mRNA was not observed. Increased LLS counts were closely correlated with increased DRG IL-31RA mRNA expression, but not with cutaneous IL-31 mRNA, in NC/Nga and BALB/c mice. Moreover, these phenomena were also observed in W/Wv and Scid mice after 2 weeks of cohousing with skin-lesioned NC/Nga mice. DRG IL-31RA expression of CNV-NC/Nga mice were significant higher than those of SPF-NC/Nga mice. A single dose of IL-31 significantly increased LLS counts more clearly in CNV-NS/Nga than SPF-NC/Nga mice. These results suggest that IL-31-induced LLS is enhanced by DRG IL-31RA expression in mice, and cohoused induced itching is regulated by DRG IL-31RA expression as in the case of itching induced by repeated administration of IL-31.
      PubDate: 2014-12-19
      DOI: 10.14800/ip.467
      Issue No: Vol. 3 (2014)
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