Frey Hairs Research Articles

Reversal of thermal and mechanical allodynia with pregabalin in a mouse model of oxaliplatin-induced peripheral neuropathy

Abstract Aims Chemotherapy-induced peripheral neuropathy (CIPN) is a dose limiting side effect in the use of the platinum-based antineoplastic drug oxaliplatin as a treatment for colorectal cancer. Currently there is no treatment available to reverse the neurotoxicity which presents as pain, sensory loss and cold allodynia in up to 80% of patients. The aim of this study is to investigate if pregabalin can reverse the allodynia caused by oxaliplatin in CIPN. Methods CIPN was induced in 10 male C57BL/6 mice (6 weeks-old) with a single intraperitoneal injection of oxaliplatin (15 mg/kg i.p.). Signs of thermal and mechanical allodynia were assessed from baseline to 20 days after injection by Cold/Hot plate (Bioseb, France) at 20 °C and hand-held von Frey (vF) hairs of gradually increasing weights. Pregabalin (3 mg/kg and 10 mg/kg p.o.) was administered to treat CIPN. Results Mechanical and thermal allodynia were established 3 days post-oxaliplatin injection and remained stable for 14 days. At day 15, pregabalin (3 mg/kg p.o.) reversed mechanical allodynia to baseline scores at 2 h (H) post-dosing and thermal allodynia at 1 and 2H post-dosing. Following a 2-day wash out where scores returned to neuropathic baseline, pregabalin (10 mg/kg p.o.) reverted scores for mechanical and thermal allodynia to baseline scores at both 1 and 2H. Thermal testing was performed either immediately after vF or alone and our results were similar, showing no iatrogenic effects of vF on thermal sensitivity. Correlation analysis of the responses to thermal and mechanical stimuli showed no significant trend, indicating that oxaliplatin-induced peripheral neuropathy affects the mechanical and thermal modalities in different ways. Conclusion Oxaliplatin-induced peripheral neuropathy as measured by thermal and mechanical allodynia is reversible by a single dose of pregabalin. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No. 642720. RM is funded by a Marie Sklodowska-Curie grant agreement No. 642720 doing a joint PhD with the Royal Veterinary Collage and Transpharmation Ltd. AF and NU are employees of Transpharmation Ltd.

Sensitivity and specificity of von Frey's hairs for the diagnosis of peripheral neuropathy in patients with type 2 diabetes mellitus

ObjectiveThe aim was to evaluate von Frey's hairs as a diagnostic tool for peripheral neuropathy in type-2 diabetes patients with symptoms typical for diabetic neuropathy with respect to nerve conduction studies (NCSs) and a combination of clinical examination and NCS. Patients and Methods65 patients with type-2 diabetes (33 men) with mean age 62.1 (SD 6.5) years, mean diabetes duration 17.5 (SD 9) years and mean symptom duration 5.2 (SD 4.3) years were examined with the set of von Frey's hairs. Diabetic neuropathy was diagnosed trough Neuropathy Disability Score (NDS). NCSs were performed on ulnar, peroneal, tibial and sural nerves. ResultsSensitivity of von Frey's hairs vs. NCS as the gold standard ranged from 37% to 79% and specificity from 65% to 87%. Sensitivity vs. combination of NDS and NCS ranged from 38% to 85% and specificity from 62% to 85%. ConclusionsVon Frey's hairs have moderate sensitivity and specificity for diagnosis of neurophysiological and also clinical neuropathy. Being a fast and easy-to-perform procedure, they could be appropriate as a screening test in clinical practice.

Von Frey's hairs – a review of their technology and use – a novel automated von Frey device for improved testing for hyperalgesia

We describe a device which allows the mechanical sensitivity of trigeminovascular sensory neurons to be monitored over extended time periods. The device can be used to stimulate either the skin or dura mater and consists of a solenoid-driven plunger to which are fixed interchangeable von Frey hairs. The solenoid can be attached to a stereotaxic carrier and mounted on a stereotaxic frame to allow precise positioning over the receptive field. The device is driven from the synchronization signals of a standard stimulator via TTL circuitry and a relay driver, to allow stimulation by a single or multiple stimuli. The advantages of the device over manual stimulation include the reproducibility of the site of stimulation; the ability to apply a known force for a known time; the ability to measure response latencies to millisecond precision and to compare them to latencies to other stimuli and; easy interface with computer-control. We discuss some of the drawbacks of the von Frey system as usually used and illustrate the use of the new device with results from experiments on peripherally induced sensitization.

The results of microneurosurgery of the inferior alveolar and lingual nerve

Purpose: The goal was to evaluate the experience of one surgical unit during a 5-year period in the evaluation and management of patients with injuries of the inferior alveolar and lingual nerve with particular reference to indications for and results of microneurosurgery. Patients and methods: This study includes all patients referred with a diagnosis of injury to the inferior alveolar or lingual nerve during 5-year period from January 1, 1994, to January 1, 1999. All patients were evaluated with Frey's hairs for touch and direction sense, 2-point discrimination, and hot and cold water and Minnesota thermal discs for temperature sensation. Patients who fulfilled certain specified criteria were offered microneurosurgery, and the results were evaluated for those who underwent microneurosurgery. Results: The study consisted of 880 consecutive patients; 96 were thought to fulfill the criteria for microneurosurgery. Of these, 51 underwent microneurosurgical exploration and repair. In 5 patients, no injury could be detected at surgery, and no corrective surgery was performed other than decompression. In 26 patients, excision and direct anastomosis were performed, and in an additional 20 patients, nerve gap reconstruction was performed. In 16 of these 20 patients, reconstruction was performed with an autogenous vein graft, and in 2 patients, a Gore-Tex tube graft (W.L. Gore & Associates, Inc, Flagstaff, AZ) was used to bridge the nerve gap. In 2 patients, an autogenous nerve was used. Thirty-four of the repairs were made on the lingual nerve, and 17 were made on the inferior alveolar nerve. With the use of established criteria, 10 patients were considered to have had a good improvement in sensation, 18 patients were considered to have had some improvement in sensation, and 22 patients were considered to have had no improvement in sensation; 1 patient reported an increase in dysesthesia after surgery. The semiobjective assessment of patients did not always correspond with the patients' subjective evaluation. Conclusion: In a relatively small study in selected cases, microneurosurgery can provide a reasonable result in improving sensation in the inferior alveolar and lingual nerve. More than 50% of patients experienced some improvement in sensation, and dysesthesia did not develop after surgery in any patient who did not have it before surgery. © 2002 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 60:485-489, 2002

PERMANENT NERVE INVOLVEMENT RESULTING: FROM INFERIOR ALVEOLAR NERVE BLOCKS

This is a prospective study of patients referred to a tertiary care center with permanent alteration in sensation of the inferior alveolar nerves, lingual nerves or both that could have resulted only from an inferior alveolar nerve block. Working with a subject pool of 83 patients, the researchers outlined and photographed the area of altered sensation on each patient, tested it with von Frey's hairs and two-point discrimination and tested temperature sensation and direction sense. Among a study population of 55 women and 28 men with a mean age of 41.2 years, the lingual nerve was affected in 79 percent of patients and the inferior alveolar nerve in 21 percent of patients. In 47 patients, the causative inferior alveolar nerve block was painful when administered, but to the other 36 patients [corrected], it felt like a normal injection. Of the local anesthetic agents used, prilocaine was found to be more frequently linked to cases of nerve involvement in this study. Occasionally, an inferior alveolar nerve block can result in permanent involvement of the inferior alveolar nerve, lingual nerve or both. The incidence and exact mechanism of involvement still are unknown. By extrapolation from this study, an incidence of anywhere between 1:26,762 and 1:160,571 inferior alveolar nerve blocks can be surmised to result in this complication. A difference in referral rates for male and female patients is difficult to explain. The 34 percent [corrected] incidence of dysesthesia in the patients in this study is of concern. Permanent nerve involvement after receiving an inferior alveolar nerve block is a documented but very rare complication of the inferior alveolar nerve block, and the exact mechanism involved is still unknown. Permanent nerve damage can very occasionally occur as a result of an inferior alveolar nerve block. The exact mechanism is unknown, and there is no means of prevention. Knowledge of the risks and complications of local anesthesia is essential.

Assessment of acute pain in preterm infants by evaluation of facial expression and frequency domain analysis of heart rate variability.

In ten preterm infants (postconceptional age 27-35 weeks) facial expression and heart rate variability (HRV) were investigated during three situations: (a) the infant at rest in its crib or incubator, (b) provocation of the withdrawal flexor reflex by application of von Frey's hairs, and (c) lancing and squeezing for blood sampling. Video recordings of facial expressions, mixed at random, were categorised as the baby being either undisturbed, disturbed or in pain and a detailed scoring for each situation was performed. Mean heart rate (HR) was calculated and power spectral analysis was assessed on data from segments of 45-s duration from the three procedures. Flexor withdrawal did not evoke visual signs of pain or influence HRV, but caused a slight increase in HR. The lancing and squeezing of the heel evoked a facial expression of pain in all infants. The HR increased and a reduction in both total HRV and power in the low frequency band of the HRV spectrum was seen during blood sampling. The differentiation between painful and non-painful procedures was more apparent when principal component analysis of HRV was applied.

Relationship Between the Anatomic and Dermatomic Levels of Spinal Cord Tumors in the Thoracic Region

In neurologic examination of patients with a suspected compressive lesion at the thoracic region, the dermatomic level of sensory disturbance is the only index indicating the anatomic level of a lesion. Because spinal cord tumors usually are solitary compressive lesions, the relationship between the anatomic and dermatomic levels is conveniently examined. We examined the relationship between the highest dermatomic level of sensory disturbance and the anatomic level, axial location, and type of spinal cord tumors in the thoracic region in 19 patients (8 men and 11 women aged 27-78 years; 11 neurinomas, 7 meningiomas, 1 neurofibroma). The distribution of sensory disturbance was evaluated with 3-g Frey hair and 1-g pin-prick examinations. The dermatomic distribution of sensory disturbance was diagnosed according to the dermatome chart of Keegan and Garrett. The anatomic level and axial location of the tumor were highly related to the sensory disturbance. Eight of 12 tumors in which the dermatomic level of sensory disturbance was within one vertebral segment of the anatomic level were situated in the middle or lower thoracic region (T6-T10). All five tumors in which the dermatomic level was two or more vertebral segments away from the anatomic level were situated at the conus medullaris (T12) or upper thoracic region (T1-T5); the highest level of sensory disturbance was from 4 to 11 segments below the anatomic level of the tumor. In two patients with no sensory disturbance, the tumor was in the upper thoracic region (T5) and compressed the spinal cord from the dorsal side. When a spinal cord tumor at the thoracic region is suspected, imaging examinations should be performed sufficiently cranially.

Response of hip joint afferent fibers to pressure and vibration in the cat

Mechanical properties of 33 slowly adapting and 8 quickly adapting capsule receptors of the hip joint were investigated. All the slowly adapting receptors identified were of a limited range, discharging only when the femur was rotated to its limit of movement. They behaved as single-spot high-threshold pressure receptors as shown by the von Frey's hairs. In addition they showed a low sensitivity to vibratory stimuli applied perpendicularly to their receptive field. Only 14 out of 33 units were found to discharge following vibration; 11 could be driven 1:1 at different frequencies. There was a general trend to be entrained at lower amplitudes for higher frequencies of vibration. A positive correlation between the pressure threshold and both activation angle and vibration threshold was found. The mechanical properties of all the quickly adapting capsule receptors were found to be similar to those described in other tissues. Finally, unlike joint receptors, slowly adapting muscle afferents travelling in the same hip articular nerve were highly sensitive to pressure and vibratory stimuli.

Influence of ions and chemical substances on the response of the frog's tongue to mechanical stimulation

1. 1. The fungiform papillae responded to the mechanical stimulation of either an air puff or a Frey's hair. but the filiform papillae did not. 2. 2. The integrated neural response to an air puff was greatest along the margin and at the apex of the dorsum linguae. 3. 3. More than three quarters of the mechanosensitive fibers responded to CaCl 2 application and one third responded to NaCl application. Mono- and divalent cations had various influences on the response to mechanical stimulation. 4. 4. Glucose and sucrose dissolved in distilled water depressed the response, but when dissolved in Ringer's solution had no effect. HCl and quinine-HCl depressed the mechanical response.

The effect of the adrenocorticotropic hormone on the state of the skin receptors

A study was made of the effect produced by ACTH on the state of cutaneous receptors of rabbit and frog. The hormone was administered to rabbits twice (in a dose of 5 units/kg) and to frogs once (5 units/animal). Receptors were stimulated by an automatic “toucher”, and in frog — by Frey's hairs and sulfuric acid solutions. Impulses appeaning in the skin nerve were recorded with the aid of a loop, oscillograph. Prior to this, determination of the reflex time was done in frogs after Turck. Excitability of rabbits diminished and reflex time of frogs increased after the ACTH administration. The impulse discharge considerably decreased after stimulation with an automatic “toucher”. With constant pressure by Frey's hairs receptor adaptation occurred very rapidly. The excitation threshold of tactile receptors and of receptors reacting to acid showed an essential rise, whereas the reaction of receptors to weak stimuli declined. Along with a reduction of receptor excitation there was a rise of receptor resistance to strong stimuli. In the latter instance the impulsation greatly decreased in control experiments, which did not occur after the ACTH administration.

Zur Frage einer Grundfunktion des Hirnes nach Reizhaaruntersuchungen1 bei Hirnverletzten

Zur Frage einer Grundfunktion des Hirnes nach Reizhaaruntersuchungen1 bei Hirnverletzten