scholarly journals IB4(+) nociceptors mediate persistent muscle pain induced by GDNF

2012 ◽  
Vol 108 (9) ◽  
pp. 2545-2553 ◽  
Author(s):  
Pedro Alvarez ◽  
Xiaojie Chen ◽  
Oliver Bogen ◽  
Paul G. Green ◽  
Jon D. Levine
Keyword(s):  
Eccentric Exercise ◽  
Muscle Pain ◽  
Mechanical Vibration ◽  
Neuromuscular Diseases ◽  
Mechanical Hyperalgesia ◽  
Prostaglandin E ◽  
Electrophysiological Recordings ◽  
Muscular Injury ◽  
Hyperalgesic Priming

Skeletal muscle is a well-known source of glial cell line-derived neurotrophic factor (GDNF), which can produce mechanical hyperalgesia. Since some neuromuscular diseases are associated with both increased release of GDNF and intense muscle pain, we explored the role of GDNF as an endogenous mediator in muscle pain. Intramuscularly injected GDNF induced a dose-dependent (0.1–10 ng/20 μl) persistent (up to 3 wk) mechanical hyperalgesia in the rat. Once hyperalgesia subsided, injection of prostaglandin E2 at the site induced a prolonged mechanical hyperalgesia (>72 h) compared with naïve rats (<4 h; hyperalgesic priming). Selective neurotoxic destruction of IB4(+) nociceptors attenuated both GDNF hyperalgesia and hyperalgesic priming. Ergonomic muscular injury induced by eccentric exercise or mechanical vibration increased muscle GDNF levels at 24 h, a time point where rats also exhibited marked muscle hyperalgesia. Intrathecal antisense oligodeoxynucleotides to mRNA encoding GFRα1, the canonical binding receptor for GDNF, reversibly inhibited eccentric exercise- and mechanical vibration-induced muscle hyperalgesia. Finally, electrophysiological recordings from nociceptors innervating the gastrocnemius muscle in anesthetized rats, revealed significant increase in response to sustained mechanical stimulation after local GDNF injection. In conclusion, these data indicate that GDNF plays a role as an endogenous mediator in acute and induction of chronic muscle pain, an effect likely to be produced by GDNF action at GFRα1 receptors located in IB4(+) nociceptors.

Role of Histamine H3 and H4 Receptors in Mechanical Hyperalgesia following Peripheral Nerve Injury

2007 ◽  
Vol 14 (6) ◽  
pp. 317-325 ◽  
Author(s):  
Fiona M. Smith ◽  
Hila Haskelberg ◽  
David J. Tracey ◽  
Gila Moalem-Taylor
Keyword(s):  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Mechanical Hyperalgesia

scholarly journals Accumulation of Prostacyclin in Rat Brain during Haemorrhagic Hypotension—Possible Role of PGI2 in Autoregulation

1984 ◽  
Vol 4 (1) ◽  
pp. 107-109 ◽  
Author(s):  
E. Shohami ◽  
A. Sidi
Keyword(s):  
Blood Pressure ◽  
Steady State ◽  
Control Group ◽  
Prostaglandin E ◽  
Cortical Tissue ◽  
Arterial Blood ◽  
Haemorrhagic Hypotension ◽  
Potent Vasodilator ◽  
Prostaglandin F

The effect of haemorrhagic hypotension on the levels of prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and 6-keto prostaglandin F1α (6-keto-PGF1α) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normotensive rats. No significant change was found in the levels of PGE2 and TXB2. The level of 6-keto-PGF1α increased from 7.8 ± 0.9 to 14.1 ± 1.9 pg/mg protein (p < 0.02) at 80 mm Hg. Our findings suggest that prostacyclin, which is a potent vasodilator, might play a role in setting the lower limit of the autoregulation range.

Dynamic Splints, Functionally-Customized With Nitinol, Can Reduce Joint Rigidity in Pediatric Subjects With Spasticity

2013 ◽  
Author(s):  
Lorenzo Garavaglia ◽  
Elena Beretta ◽  
Sandra Strazzer ◽  
Felice Sala ◽  
Morena Delle Fave ◽  
...  
Keyword(s):  
Niti Alloy ◽  
Neuromuscular Diseases ◽  
Contact Forces ◽  
Muscle Rigidity ◽  
Cortical Function ◽  
Paretic Limb ◽  
Limb Posture ◽  
Joint Rigidity ◽  
Complex Phenomena

Neuromuscular diseases as a consequence of brain damage are complex phenomena involving disuse, immobility, brain tissue remodeling and cortical function remapping. They may have various causes and strike any part of the population. The vicious circle leading to a worsening of the patients’ conditions proceeds through muscle shortening by contractures, disruption of the normal reflex behavior and sensory problems, development of spasticity [1]. Physical rehabilitation alone or in association with surgery or pharmacological treatments can be useful in limiting those degenerations. Besides manual rehabilitation, splints and braces are prescribed to control the limb posture and obtain stretching of the muscles. The role of those orthoses is to maintain the paretic limb in a set ‘physiological’ position and let it relax into that posture, in an attempt to reduce muscle rigidity and contractures. However applying a fixed constraint to the limb and waiting for relaxation to take place, may cause discomfort, pain, skin rash, and sundry different complications [2]. Also, any residual voluntary movement is prevented by a fixed-angle splinting. In addition, all these negative characteristics limit tolerability and daily application times. This work presents a different way to promote limb repositioning, based on the application of NiTi-alloy-based dynamic splints, which favor mobility and any residual use of the affected limb. Furthermore it suggests that application of mild contact forces prolonged in time has the advantage of feeling less painful and uncomfortable for the patients, improving overall treatment tolerability.

Pro-inflammatory and vasoconstricting prostanoid PGF2α causes no headache in man

Cephalalgia ◽  
2011 ◽  
Vol 31 (15) ◽  
pp. 1532-1541 ◽  
Author(s):  
Maria Antonova ◽  
Troels Wienecke ◽  
Jes Olesen ◽  
Messoud Ashina
Keyword(s):  
Healthy Volunteers ◽  
Rating Scale ◽  
Superficial Temporal Artery ◽  
Area Under The Curve ◽  
Temporal Artery ◽  
Human Model ◽  
Prostaglandin E ◽  
Signalling Molecules ◽  
Prostaglandin F

Background: During two decades of migraine provocation studies with naturally occurring signalling molecules, vasodilators such as prostaglandin E2, prostaglandin I2 (prostacyclin) and prostaglandin D2 were shown to be able to induce headache in man. To elucidate the role of inflammation and vasodilatation in the generation of headache, we investigated whether the pro-inflammatory and vasoconstricting prostanoid prostaglandin F2α (PGF2α) would cause headache in a human model of headache. Methods: Twelve healthy volunteers were randomly allocated to receive 3.5 µg/kg/min PGF2α or placebo over 20 min in a two-way crossover study. We recorded headache intensity on a verbal rating scale, middle cerebral artery blood flow velocity (VMCA) and the diameters of the superficial temporal artery (STA) and radial artery (RA). Results: We found no difference in the area under the curve (AUC) for immediate headache (0–90 min) between PGF2α and placebo ( p = 0.144). The McNemar's test showed no difference in the incidence of immediate and delayed headache between verum and placebo ( p = 0.500 and p = 1.000, respectively). There was no difference in VMCA ( p = 0.776) and in the diameter of the STA ( p = 0.460) or RA ( p = 0.780) between PGF2α and placebo. Conclusion: The present study shows that PGF2α, unlike vasodilating prostaglandins, does not provoke headache. We suggest that the vasodilating abilities of prostaglandins are important for the induction of experimental headache in healthy volunteers.

Effect of Caffeine on Leg-Muscle Pain during Intense Cycling Exercise: Possible Role of Anxiety Sensitivity

2008 ◽  
Vol 18 (2) ◽  
pp. 103-115 ◽  
Author(s):  
Rachael C. Gliottoni ◽  
Robert W. Motl
Keyword(s):  
Pain Intensity ◽  
Anxiety Sensitivity ◽  
High Intensity ◽  
Muscle Pain ◽  
Caffeine Ingestion ◽  
Cycling Exercise ◽  
College Age ◽  
Peak Aerobic Capacity ◽  
Leg Muscle

This experiment examined the effect of a moderate dose of caffeine on perceptions of leg-muscle pain during a bout of high-intensity cycling exercise and the role of anxiety sensitivity in the hypoalgesic effect of caffeine on muscle pain during exercise. Sixteen college-age women ingested caffeine (5 mg/kg body weight) or a placebo and 1 hr later completed 30 min of cycling on an ergometer at 80% of peak aerobic capacity. The conditions were completed in a counterbalanced order, and perceptions of leg-muscle pain were recorded during the bouts of exercise. Caffeine resulted in a large reduction in leg-muscle pain-intensity ratings compared with placebo (d = −0.95), and the reduction in leg-muscle pain-intensity ratings was larger in those with lower anxiety-sensitivity scores than those with higher anxiety-sensitivity scores (d = −1.28 based on a difference in difference scores). The results support that caffeine ingestion has a large effect on reducing leg-muscle pain during high-intensity exercise, and the effect is moderated by anxiety sensitivity.

Muscle pain in myophosphorylase deficiency (McArdle’s disease): The role of gender, genotype, and pain-related coping

Pain ◽  
2006 ◽  
Vol 124 (3) ◽  
pp. 295-304 ◽  
Author(s):  
Oliver Rommel ◽  
Rudolf A. Kley ◽  
Gabriele Dekomien ◽  
Jörg T. Epplen ◽  
Matthias Vorgerd ◽  
...  
Keyword(s):  
Muscle Pain ◽  
Mcardle's Disease ◽  
Mcardle’S Disease

scholarly journals Role of Prostaglandin E Receptor EP 1 Subtype in the Development of Renal Injury in Genetically Hypertensive Rats

Hypertension ◽  
2003 ◽  
Vol 42 (6) ◽  
pp. 1183-1190 ◽  
Author(s):  
Takayoshi Suganami ◽  
Kiyoshi Mori ◽  
Issei Tanaka ◽  
Masashi Mukoyama ◽  
Akira Sugawara ◽  
...  
Keyword(s):  
Renal Injury ◽  
Prostaglandin E ◽  
Hypertensive Rats ◽  
Genetically Hypertensive Rats ◽  
Genetically Hypertensive

scholarly journals Clinical Implications High Frequency Chest Wall Oscillation (HFCWO)

2012 ◽  
Vol 1 (1) ◽  
Author(s):  
E. Mantellini ◽  
L. Perrero ◽  
S. Petrozzino ◽  
A. Gatta ◽  
S. Bona
Keyword(s):  
Chest Wall ◽  
High Frequency ◽  
Neuromuscular Disease ◽  
Respiratory Infections ◽  
Neuromuscular Diseases ◽  
Correct Treatment ◽  
Bronchial Secretions ◽  
High Incidence ◽  
Wall Oscillation

Purpose: patients with neuromuscular diseases presents an high incidence of respiratory infections favoured by stagnation of deep bronchial secretions and deficit of cough. The aim of the study is to evaluate the correct treatment of this condition and the role of High Frequency Chest Wall Oscillation (HFCWO) in helping the removal of bronchial secretions and reduce the incidence of infections in patients with neuromuscular disease. Methods: analysis of the current bibliography related to respiratory infections and neuromuscular disease. PCEF (Peak Cough Expiratory Flow) is used as a standardized indicator of efficiency of cough. Results: the High Frequency Chest Wall Oscillation (HFCWO) is useful, in cases of increased production of mucus and impairment of muco-ciliary clearance, to remove the tracheobronchial secretions and reduce the incidence of infections. Conclusions: the correct approach to patients with neuromuscular disease and frequent respiratory infections is focused on treatment of cough ineffective and management of bronchial secretions. High Frequency Chest Wall Oscillation (HFCWO) (VEST) has a central role in treatment of cough ineffective and management of bronchial secretions reducing respiratory infections.

The transmembrane adaptor protein NTAL limits mast cell chemotaxis toward prostaglandin E2

2018 ◽  
Vol 11 (556) ◽  
pp. eaao4354 ◽  
Author(s):  
Ivana Halova ◽  
Monika Bambouskova ◽  
Lubica Draberova ◽  
Viktor Bugajev ◽  
Petr Draber
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Adaptor Protein ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
And Function ◽  
Cell Chemotaxis

Chemotaxis of mast cells is one of the crucial steps in their development and function. Non–T cell activation linker (NTAL) is a transmembrane adaptor protein that inhibits the activation of mast cells and B cells in a phosphorylation-dependent manner. Here, we studied the role of NTAL in the migration of mouse mast cells stimulated by prostaglandin E2 (PGE2). Although PGE2 does not induce the tyrosine phosphorylation of NTAL, unlike IgE immune complex antigens, we found that loss of NTAL increased the chemotaxis of mast cells toward PGE2. Stimulation of mast cells that lacked NTAL with PGE2 enhanced the phosphorylation of AKT and the production of phosphatidylinositol 3,4,5-trisphosphate. In resting NTAL-deficient mast cells, phosphorylation of an inhibitory threonine in ERM family proteins accompanied increased activation of β1-containing integrins, which are features often associated with increased invasiveness in tumors. Rescue experiments indicated that only full-length, wild-type NTAL restored the chemotaxis of NTAL-deficient cells toward PGE2. Together, these data suggest that NTAL is a key inhibitor of mast cell chemotaxis toward PGE2, which may act through the RHOA/ERM/β1-integrin and PI3K/AKT axes.

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