The Assessment of Nipple Areola Complex Sensation with Semmes-Weinstein Monofilaments—Normative Values and Its Covariates

Objective: To establish normative data for nipple-areola complex (NAC) sensibility examined with Semmes-Weinstein monofilament test (SWMT) and two-point discrimination (TPD) in women with varying breast sizes, including women with gigantomastia. We also aimed to identify clinical variables influencing NAC sensation. Methods: A total of 320 breasts in 160 Caucasian women (mean age 33.6 years, SD 11 years) were examined (including 50 hypertrophic breasts). NACs sensation was examined using Semmes-Weinstein monofilaments (SWM) and the Weber Two-Point Discrimination Test. Results: The nipple appeared to be the most sensitive part of NAC. In normal-sized breasts, sensation thresholds (SWM) correlated with: age, BMI, history of births, breast size and ptosis (for all locations), breastfeeding history (for nipple and upper areola) and areola diameter (for all locations apart from the nipple). Regression analysis showed that age, cup size and suprasternal notch-to-nipple distance are risk factors for diminished NAC sensation. Sensation thresholds in all NAC locations of hypertrophic breasts were significantly higher compared to normal-sized breasts, while TPD tests did not differ between the groups. Conclusions: We provided normative values of NAC sensation (tactile threshold and TPD) for different NAC areas. Our investigation indicated that SWM are useful diagnostic tools when the following factors are considered while examining NAC sensation: location (nipple vs. areola), age, breast size, suprasternal notch-to-nipple distance, history of births and breastfeeding. Hypertrophic breasts presented significantly higher sensation thresholds for all NAC locations. The report may serve as a reference data for further investigations regarding NAC sensation after different breast surgeries.

5-HT7 Receptor Is Involved in Electroacupuncture Inhibition of Chronic Pain in the Spinal Cord

Knee osteoarthritis (KOA) is a common and disabling condition characterized by attacks of pain around the joints, and it is a typical disease that develops chronic pain. Previous studies have proved that 5-HT1, 5-HT2, and 5-HT3 receptors in the spinal cord are involved in electroacupuncture (EA) analgesia. The 5-HT7 receptor plays antinociceptive role in the spinal cord. However, it is unclear whether the 5-HT7 receptor is involved in EA analgesia. The 5-HT7 receptor is a stimulatory G-protein (Gs)-coupled receptor that activates adenylyl cyclase (AC) to stimulate cyclic adenosine monophosphate (cAMP) formation, which in turn activates protein kinase A (PKA). In the present study, we found that EA significantly increased the tactile threshold and the expression of the 5-HT7 receptor in the dorsal spinal cord. Intrathecal injection of 5-HT7 receptor agonist AS-19 mimicked the analgesic effect of EA, while a selective 5-HT7 receptor antagonist reversed this effect. Moreover, intrathecal injection of AC and PKA antagonists prior to EA intervention prevented its anti-allodynic effect. In addition, GABAA receptor antagonist bicuculline administered (intrathecal, i.t.) prior to EA intervention blocked the EA effect on pain hypersensitivity. Our data suggest that the spinal 5-HT7 receptor activates GABAergic neurons through the Gs–cAMP–PKA pathway and participates in EA-mediated inhibition of chronic pain in a mouse model of KOA.

Correlation Between Lower And Higher Order Sensory Functions And Fine And Gross Motor Function In Dominant And Non-Dominant Hand Of Patients With Choronic Stroke

Introduction: To investigate the correlation between lower and higher order sensory functions and manual dexterity as well as Identify factors affecting upper extremity motor function(UEMF) in subjects with chronic stroke.Methods: In this correlational study, seventy chronic stroke subjects (48 male and 22 female) by mean age of 56.94 (±12.92) years and mean time after stroke of 3.01 (±2.64) years were selected by simple nonprobability method. Lower order sensory function (i.e., light touch threshold), higher order sensory functions (i.e., tactile acuity, weight and texture discrimination, haptic performance and wrist proprioception) were measured by Weinstein enhanced sensory test, two point discrimination, wrist position sense test, hand active sensation test and haptic object test, respectively. The gross and fine manual dexterity were measured by Wolf Motor Function Test (WMFT), Box and Block Test(BBT) and Purdue Pegboard (PPB) test. The step by step regression model was used to investigate the sensory determinants of motor function.Results: A weak to high significant correlation (r =0.25 to 0.80) was found between sensory predictors and motor outcomes. The regression models explained 19.8%, 30.3% and 52.3% of variancein motor function measures of the PPB, BBT and WMFT, respectively. The tactile threshold (p<0.001) was the most relevant predictor in all stepwise models for all motor outcomes in dominant or non-dominant hand , followed by tactile acuity, haptic performance and wrist proprioception (p< 0.05). The weight and texture discrimination was not included in any outcome models.Conclusion: The results of present study showed that tactile threshold as lowr order sensory function is the most relevant predictor for UEMF in stroke. The results reinforce that rehabilitation interventions focused on tactile threshold may be best able to impact UEMF in stroke subjects.

Correlation Between Lower And Higher Order Sensory Functions And Fine And Gross Motor Function In Dominant And Non-Dominant Hand Of Patients With Choronic Stroke

Introduction: To investigate the correlation between lower and higher order sensory functions and manual dexterity as well as Identify factors affecting upper extremity motor function(UEMF) in subjects with chronic stroke.Methods: In this correlational study, seventy chronic stroke subjects (48 male and 22 female) by mean age of 56.94 (±12.92) years and mean time after stroke of 3.01 (±2.64) years were selected by simple nonprobability method. Lower order sensory function (i.e., light touch threshold), higher order sensory functions (i.e., tactile acuity, weight and texture discrimination, haptic performance and wrist proprioception) were measured by Weinstein enhanced sensory test, two point discrimination, wrist position sense test, hand active sensation test and haptic object test, respectively. The gross and fine manual dexterity were measured by Wolf Motor Function Test (WMFT), Box and Block Test(BBT) and Purdue Pegboard (PPB) test. The step by step regression model was used to investigate the sensory determinants of motor function.Results: A weak to high significant correlation (r =0.25 to 0.80) was found between sensory predictors and motor outcomes. The regression models explained 19.8%, 30.3% and 52.3% of variancein motor function measures of the PPB, BBT and WMFT, respectively. The tactile threshold (p<0.001) was the most relevant predictor in all stepwise models for all motor outcomes in dominant or non-dominant hand , followed by tactile acuity, haptic performance and wrist proprioception (p< 0.05). The weight and texture discrimination was not included in any outcome models. Conclusion: The results of present study showed that tactile threshold as lowr order sensory function is the most relevant predictor for UEMF in stroke. The results reinforce that rehabilitation interventions focused on tactile threshold may be best able to impact UEMF in stroke subjects.

A Pilot Study of a Tactile Measurement System Using Lateral Skin Stretch on Foot Plantar Surface

The purpose of this study is to develop smart equipment to quantify plantar tactile sensibility for early diagnosis and tracking of peripheral neuropathy caused by diabetes mellitus. In this paper, we present new testing equipment composed of a plantar tactile stimulation platform with a moving contactor to stretch the skin tangentially, a response switch for each tactile stimulus, a motor control box, and a personal computer for psychophysical data processing. This testing equipment offers more precise measurements and is easy to use compared to conventional testing tools such as von Frey monofilaments, pin-prick testing devices, and current perception threshold testers. Using our testing equipment, we showed that the plantar tactile threshold for the tangential stretching stimulus on the first metatarsal head of the feet ranges from approximately 10 to 60 μm for subjects without diabetic foot problems. Meanwhile, the plantar tactile threshold of some subjects suspected of having diminished protective sensation by the Semmens-Weinstein monofilament testing is approximately 100 μm or more. These preliminary results suggest that our testing equipment based on the plantar sensation elicited by lateral stretching of skin has the potential for quantitative diagnosis in subjects suspected of suffering from neuropathy, and for monitoring changes over time to sustain quality of life.

The effect of connexin 36 deletion on chemotherapy-induced peripheral neuropathy (CIPN).

1 Background: CIPN is a debilitating side effect and dose limiting toxicity of many chemotherapeutic agents. CIPN induces pathological changes in dorsal root ganglia (DRG), leading to increased cross-talk among the glia that surround sensory neurons (Satellite Glial Cells, SGC’s) and between sensory neurons and their adjacent SGCs via gap junctions. Since Connexin 36 (Cx36) is the main neuronal gap junction protein, we investigated CIPN in mice with deletion of Cx36. Methods: To induce CIPN, mice were given two i.p. oxaliplatin (oxa) injections 2 days apart. Controls received saline (sal). We used transgenic mice, which were either heterozygous for Cx36 or complete Cx36 knockouts (Cx36 Het or Cx36 KO), and littermate controls (Cx36 wildtype), 6-14 per group. Tactile sensitivity of the hindpaws was assessed prior to and every week after injections for 4 weeks using von Frey filaments. The number of paw withdrawals to 10 stimulations with each filament and pain thresholds (corresponding to filament that elicits 8/10 responses) were recorded. Results: Oxa-injected wildtype mice had higher response rates to filaments compared to sal-injected controls (p < 0.05), and lower tactile thresholds (at 9 days: sal 6.0±0.0g vs. oxa 1.9±0.5g, p < 0.0001), indicating hypersensitivity. Compared with wildtype, mice lacking Cx36 (Cx36 KO) displayed significantly less tactile hypersensitivity after oxa (tactile threshold at 9 days: WT 1.9±0.5g vs. KO 4.0±0.4g, p < 0.01), whereas oxa induced tactile hypersensitivity occurred in a similar fashion in Cx36 Het mice (tactile threshold at 9 days: WT 1.9±0.5g vs. Het 1.5±0.1g). At 9 days, there were fewer responses to filaments in oxa-injected Cx36 KO mice compared to oxa-injected wildtype mice (p < 0.05), but not in oxa-injected Cx36 Het mice. Conclusions: We found that oxaliplatin induces transient CIPN, represented by tactile hypersensitivity, in wildtype mice. Deletion of the gap junction protein Cx36, as displayed in the Cx36 KO mice, resulted in significantly less CIPN. This is the first report that a neuronal gap junction protein may modulate pain sensitivity, and points to a new molecule (Cx36) as a potential novel target for CIPN therapy.

The role of pannexin 1 in chemotherapy-induced peripheral neuropathy (CIPN).

6 Background: CIPN is a debilitating side effect and dose limiting toxicity of anticancer drug therapies. CIPN induces pathological changes in dorsal root ganglia (DRG), leading to increased cross-talk between sensory neurons and satellite glial cells (SGCs), specifically ATP mediated SGC-neuron signaling. We therefore investigated CIPN in mice with neuron- or glia-specific deletion of the ATP-releasing channel Pannexin 1 (Panx 1). Methods: To induce CIPN, mice were given two i.p. oxaliplatin (oxa) injections two days apart. Controls received saline (sal). We used C57Bl6 wildtype and transgenic mice with neuron- or glia-specific Panx1 deletion (NFHcre or GFAPcre:Panx1F/F) and littermate controls (Panx1F/F), 7-11 per group. Tactile sensitivity of the hindpaws was assessed prior to and every week after injections for 3 weeks using von Frey filaments. The number of paw withdrawals to 10 stimulations with each filament and pain thresholds (corresponding to filament that elicits 8/10 responses) were recorded. Overall mouse condition was assessed using Open Field Tests. Results: C57Bl6 mice developed transient tactile hypersensitivity after oxa injection, which was most prominent at day 9 and ceased at day 21. Oxa-injected mice had lower tactile thresholds (at 9 days: sal 5.5±0.3g vs. oxa 2.7±0.4g, p < 0.001) and higher response rates to filaments compared to sal-injected controls (p < 0.05), but revealed no changes in any other behavior. Mice with glia-specific Panx1 deletion did not display significant tactile hypersensitivity at any time after oxa (tactile threshold at 9 days: sal 5.5±0.3g vs. oxa 5.8±0.2g), whereas oxa induced tactile hypersensitivity did occur in mice with neuron-specific Panx1 deletion (at 9 days: sal 6±0g vs. oxa 1.3±0g, p < 0.0001) and Panx1F/F littermates (at 9 days: sal 6.0±0g vs. oxa 1.3±0.1g, p < 0.0001). Conclusions: We found that oxaliplatin induces transient CIPN, but no other behavioral changes in wildtype mice. Deletion of the ATP-releasing channel Panx1 in glia, but not in neurons, prevented CIPN development. This points to a new molecule (Panx1) and a new cell type (glia) as potential novel targets for pain therapy.