Expression of Opioid Receptors in Cells of the Immune System

The observation of the immunomodulatory effects of opioid drugs opened the discussion about possible mechanisms of action and led researchers to consider the presence of opioid receptors (OR) in cells of the immune system. To date, numerous studies analyzing the expression of OR subtypes in animal and human immune cells have been performed. Some of them confirmed the expression of OR at both the mRNA and protein level, while others did not detect the receptor mRNA either. Although this topic remains controversial, further studies are constantly being published. The most recent articles suggested that the expression level of OR in human peripheral blood lymphocytes could help to evaluate the success of methadone maintenance therapy in former opioid addicts, or could serve as a biomarker for chronic pain diagnosis. However, the applicability of these findings to clinical practice needs to be verified by further investigations.     

Functional Coupling of Slack Channels and P2X3 Receptors Contributes to Neuropathic Pain Processing

The sodium-activated potassium channel Slack (K_Na1.1, Slo2.2, or Kcnt1) is highly expressed in populations of sensory neurons, where it mediates the sodium-activated potassium current (I_KNa) and modulates neuronal activity. Previous studies suggest that Slack is involved in the processing of neuropathic pain. However, mechanisms underlying the regulation of Slack activity in this context are poorly understood. Using whole-cell patch-clamp recordings we found that Slack-mediated I_KNa in sensory neurons of mice is reduced after peripheral nerve injury, thereby contributing to neuropathic pain hypersensitivity. Interestingly, Slack is closely associated with ATP-sensitive P2X3 receptors in a population of sensory neurons. In vitro experiments revealed that Slack-mediated I_KNa may be bidirectionally modulated in response to P2X3 activation. Moreover, mice lacking Slack show altered nocifensive responses to P2X3 stimulation. Our study identifies P2X3/Slack signaling as a mechanism contributing to hypersensitivity after peripheral nerve injury and proposes a potential novel strategy for treatment of neuropathic pain.     

Mitochondrial Bioenergetic,Photobiomodulation and Trigeminal Branches Nerve Damage,What’s the Connection? A Review

Background: Injury of the trigeminal nerve in oral and maxillofacial surgery can occur. Schwann cell mitochondria are regulators in the development, maintenance and regeneration of peripheral nerve axons. Evidence shows that after the nerve injury, mitochondrial bioenergetic dysfunction occurs and is associated with pain, neuropathy and nerve regeneration deficit. A challenge for research is to individuate new therapies able to normalise mitochondrial and energetic metabolism to aid nerve recovery after damage. Photobiomodulation therapy can be an interesting candidate, because it is a technique involving cell manipulation through the photonic energy of a non-ionising light source (visible and NIR light), which produces a nonthermal therapeutic effect on the stressed tissue. Methods: The review was based on the following questions: (1) Can photo-biomodulation by red and NIR light affect mitochondrial bioenergetics? (2) Can photobiomodulation support damage to the trigeminal nerve branches? (preclinical and clinical studies), and, if yes, (3) What is the best photobiomodulatory therapy for the recovery of the trigeminal nerve branches? The papers were searched using the PubMed, Scopus and Cochrane databases. This review followed the ARRIVE-2.0, PRISMA and Cochrane RoB-2 guidelines. Results and conclusions: The reliability of photobiomodulatory event strongly bases on biological and physical-chemical evidence. Its principal player is the mitochondrion, whether its cytochromes are directly involved as a photoacceptor or indirectly through a vibrational and energetic variation of bound water: water as the photoacceptor. The 808-nm and 100 J/cm² (0.07 W; 2.5 W/cm²; pulsed 50 Hz; 27 J per point; 80 s) on rats and 800-nm and 0.2 W/cm² (0.2 W; 12 J/cm²; 12 J per point; 60 s, CW) on humans resulted as trustworthy therapies, which could be supported by extensive studies.     

Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ET_B) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ET_B receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ET_B receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ET_B-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ET_B receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ET_B receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.     

Thermal radiative protection of fire fighters' protective clothing

A method for measuring the thermal radiative protection of actual fire fighters' garments to an incident radiative heat flux of 8.4 kW/m² is described. Typical results obtained with several conventional and prototype garments are presented. These results indicate the time to pain, and second degree burn as well as the pain alarm time. The thermal inertia of the garments is also measured based upon burn exposure time. Differences in physical properties such as garment thickness, total weight and number of layers are examined in order to establish the existence of any correlations.Issued as NRCC 26171. Reference: M. Day and P. Z. Sturgeon, Thermal Radiative Protection of Fire Fighters' Protective Clothing,Fire Technology, Vol. 23, No. 1, February 1987, p. 49.     

Synthesis, σ Receptor Affinity,and Pharmacological Evaluation of 5‐Phenylsulfanyl‐ and 5‐Benzyl‐Substituted Tetrahydro‐2‐benzazepines

In accordance with a novel strategy for generating the 2‐benzazepine scaffold by connecting C6–C1 and C3–N building blocks, a set of 5‐phenylsulfanyl‐ and 5‐benzyl‐substituted tetrahydro‐2‐benzazepines was synthesized and pharmacologically evaluated. Key steps of the synthesis were the Heck reaction, the Stetter reaction, a reductive cyclization, and the introduction of diverse N substituents at the end of the synthesis. High σ₁ affinity was achieved for 2‐benzazepines with linear or branched alk(en)yl residues containing at least an n‐butyl substructure. The butyl‐ and 4‐fluorobenzyl‐substituted derivatives, (±)‐5‐benzyl‐2‐butyl‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepine ( 19 b ) and (±)‐5‐benzyl‐2‐(4‐fluorobenzyl)‐2,3,4,5‐tetrahydro‐1H‐2‐benzazepine ( 19 m ), show high selectivity over more than 50 other relevant targets, including the σ₂ subtype and various binding sites of the N‐methyl‐D ‐aspartate (NMDA) receptor. In the Irwin screen, 19 b and 19 m showed clean profiles without inducing considerable side effects. Compounds 19 b and 19 m did not reveal significant analgesic and cognition‐enhancing activity. Compound 19 m did not have any antidepressant‐like effects in mice.     

Short communication: Assessment of disbudding pain in dairy calves using nonlinear measures of heart rate variability

The purpose of this study was to evaluate whether pain-related stress caused by disbudding could be detected using nonlinear measures of heart rate variability (HRV). Twenty-five female Holstein calves (4–7 wk of age) were randomly assigned to 1 of 3 treatments: (1) sham disbud (SHAM; n = 9), (2) disbud with lidocaine–meloxicam pain mitigation (MED; n = 8), or (3) disbud without pain mitigation (NoMED; n = 8). Heart rate variability (sample entropy, percentage determinism, percentage recurrence, or mean length of diagonal lines in a recurrence plot) was recorded on d −1, 0, 1, 3, and 5 relative to the experimental procedure, with disbudding taking place on d 0. The short-term detrended fluctuation analysis scaling exponent was greater in MED calves than in SHAM calves, indicating a greater stress response to the disbudding procedure regardless of pain mitigation. These results indicate that calves in the MED group may have experienced pain-related stress as a result of the disbudding procedure. The remaining nonlinear HRV measures did not differ by treatment. Future research on this topic should address additional potential confounding factors, such as the effect of pain-mitigating drugs on autonomic function or the influence of the autonomic nervous system on wound healing, that may prohibit HRV measurement as an indicator of disbudding pain severity.     

Are hybrid sit–stand postures a good compromise between sitting and standing?

Potential alternatives for conventional sitting and standing postures are hybrid sit-stand postures (i.e. perching). The purposes of this study were (i) to identify where lumbopelvic and pelvic angles deviate from sitting and standing and (ii) to use these breakpoints to define three distinct postural phases: sitting, perching, and standing, in order to examine differences in muscle activations and ground reaction forces between phases. Twenty-four participants completed 19 1-min static trials, from sitting (90°) to standing (180°), sequentially in 5°trunk–thigh angle increments. The perching phase was determined to be 145–175° for males and 160–175° for females. For both sexes, knee extensor activity was lower in standing compared to perching or sitting (p < .01). Anterior–posterior forces were the highest in perching (p < .001), requiring ～15% of body-weight. Chair designs aimed at reducing the lower limb demands within 115–170° trunk–thigh angle may improve the feasibility of sustaining the perched posture.

Practitioner summary: Individuals who develop low back pain in sitting or standing may benefit from hybrid sit-stand postures (perching), yet kinematic and kinetic changes associated with these postures have not been investigated. Perching can improve lumbar posture at a cost of increased lower limb demands, suggesting potential avenues for chair design improvement.

Abbreviations: A/P: anterior-posterior; M/L: medial-lateral; LBP: low back pain; EMG: electromyography; TES: thoracic erector spinae; LES: lumbar erector spinae; VMO: vastus medialis obliquus; MVC: maximum voluntary contraction; ASIS: anterior superior iliac spine; PSIS: posterior superior iliac spine; BW: body weight; RMSE: root mean square error; SD: standard deviation; ROM: range of motion     

The time variation pattern of mechanical exposure and the reporting of low back pain

Creating mechanical exposure profiles for multi-component jobs for use in epidemiological studies of work-related musculoskeletal disorders is challenging but becoming more common. Once time-varying mechanical exposure profiles are created, some form of exposure index must be derived. Available techniques typically provide information about the relative amount of time exposed to different levels and durations of stressors. Little or no information concerning the sequence or history of exposure delivery is maintained. The current paper examines an approach to the processing of time varying exposures for epidemiological studies. Shift-long exposure data of 68 production operators (34 cases; 34 controls) from a large epidemiological study of low back pain reporting were used to create individual shift-long internal mechanical exposure profiles. These were processed through a first-order system with varying time constants to generate a range of modelled responses from which two exposure indices were then created. The utility of these mechanical exposure indices was evaluated using low back pain reporting as the health outcome from the same epidemiological study. The modelled response using the first-order system appeared to provide additional exposure information, perhaps time-history sensitive exposure information that was not captured by the unprocessed exposure profiles. Risk estimates from the peak value exposure index derived from an internal exposure processed with a time constant of 2?s were almost doubled compared with the risk estimates of the unprocessed peak value, and the final value, taken from the internal exposure processed with a time constant of 5?000?s, generated higher risk estimates over the cumulative/average exposures. This study suggests a potential analysis approach for epidemiological studies of musculoskeletal disorders where long-duration mechanical exposure data is available.