https://orcid.org/0000-0001-8536-111X
Figures
Abstract
Objective
Photobiomodulation selectively controls the activity of the sensory nervous system associated with A-delta and C fibers. Hypersensitivity involving the afferent A-delta and C fibers occurs in cystitis and decreases urinary function. This study aimed to investigate the effect of photobiomodulation on urinary storage dysfunction and voiding functions in cystitis model rats.
Methods
We prepared the rat cystitis model. Under anesthesia, a cannula was connected to the bladder via a ventral incision. 0.3% acetic acid or saline was injected into the bladder. Continuous cystometry was performed, measuring bladder pressure and voiding urine volume with rats freely mobile. Laser irradiation was applied to the L6 lumbosacral intervertebral foramen using an 830 nm laser. Residual urine was extracted post-cystometry.
Results
In the rat cystitis model groups, there was a significant decrease in the voiding interval and volume compared to the group receiving normal saline infusion. After sham or laser irradiation, only the group with laser irradiation showed a significant increase in voiding interval (217%, p = 0.0002) and voiding volume (192%, p = 0.0012) in the parameters of storage dysfunction. The basal pressure, intravesical pressure, and residual urine volume remained unchanged in all groups before and after irradiation.
Citation: Ishibashi N, Uchiyama T, Tao S (2024) Effect of photobiomodulation on lower urinary tract dysfunction in rat cystitis model. PLoS ONE 19(7): e0306527. https://doi.org/10.1371/journal.pone.0306527
Editor: Michael R. Hamblin, Massachusetts General Hospital, UNITED STATES
Received: March 25, 2024; Accepted: June 19, 2024; Published: July 26, 2024
Copyright: © 2024 Ishibashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting Information files.
Funding: International University of Health and Welfare received the grant support from Teijin Pharma Limited for another research with Dr. Uchiyama. - Dr. Uchiyama was involved in editing the content of this manuscript and advising on analysis methods.
Competing interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: [International University of Health and Welfare received the grant support from Teijin Pharma Limited for another research with Dr. Uchiyama.] This does not alter our adherence to PLOS ONE policies on sharing data and materials.
Introduction
Photobiomodulation (PBM) or low-level laser therapy (LLLT) have been used in clinical practice for several decades to treat many painful conditions [1, 2]. Over 100 randomized, double-blind, placebo-controlled clinical trials (RCTs) have been published. Many RCTs have shown positive outcomes for osteoarthritis [3], tendinopathies [4], wounds [5], back pain [6], neck pain [7], muscle fatigue [8], peripheral nerve injuries [9], and stroke [10]. Basic supportive studies investigating the mechanisms, local tissues, and systemic effects have also been published. The anti-inflammatory effects, accelerated bone nodule formation, pain relief, and nerve repair induced by laser irradiation have been reported in vitro and in vivo [2]. Some in vivo studies have reported that laser irradiation can control peripheral sensory nervous system activity associated with A-delta and C fibers [11–17].
The sensory nervous system functions as an important trigger, playing a role not only in pain perception but also in bladder control. Symptoms associated with detrusor overactivity, such as sensations of urinary urgency, pain, and frequency, have common pathological inputs, including high-level sensory nerve signals induced by tissue damage, nerve hypersensitivity, and inflammation [18, 19]. In addition, small myelinated A-delta and unmyelinated C fibers are involved in these symptoms. Some studies have indicated that detrusor overactivity is mediated by nerve hypersensitivity associated with functionalized afferent C fibers [20, 21]. It has also been reported that sensory signals from the bladder under pathological storage conditions associated with inflammation are mediated by afferent C fibers, whereas afferent A-delta fibers mediate normal signaling [22]. Controlling sensory nerve hypersensitivity associated with afferent A-delta and C fibers is important for managing symptoms associated with cystitis.
Thus, we hypothesized that PBM might improve detrusor overactivity and the urgency caused by detrusor overactivity associated with cystitis by controlling sensory nerve hypersensitivity. In addition, laser irradiation selectively decreased the peripheral nerve activity associated with afferent A-delta and C fibers [13–17]. These findings indicate the potential of PBM to control sensory nerve hypersensitivity without influencing efferent nerve activity.
We aimed to study the effects of PBM on the urinary storage dysfunction and voiding function associated with cystitis. Intravesical administration of acetic acid in rats induces a decrease in the voiding interval and bladder capacity during urine storage [20, 23]. Several studies have indicated that the urinary symptoms of acetic acid-induced cystitis in rats are mediated by nerve hypersensitivity associated with afferent A-delta and C fibers [21, 24]. We examined the effects of laser irradiation of the L6 lumbosacral nerve, which contains A-delta and C fibers that transmit the sensation of the bladder [25–27], on micturition reflex parameters in a rat model of cystitis induced by an intravesical infusion of acetic acid.
Materials and methods
Animals
Eight-week-old Sprague-Dawley (SD) male rats (Crl:CD, Charles River Co., Ltd.) were used in all experiments. The rats were kept under environmental control with a 12 h light/dark cycle (lights on at 7:00 a.m.), a temperature (permissive range) of 20–26°C, and a humidity (permissive range) of 35–60% with free access to food and water.
Preparation of animal model
The time-course of the experiment is shown in Fig 1A. The rats were anesthetized by inhalation of 2% isoflurane and maintained in the dorsal position. The bladder was exposed using a ventral incision, and a cannula (PE-50; Becton, Dickinson & Co.) was connected to the bladder dome. The other end of the cannula was passed backwards subcutaneously and sutured to the muscles and skin. Outside the body, the cannula was protected using a metal spring and connected to a siebel. Vital signs were monitored frequently from the onset of anesthesia until the rats regained consciousness. Buprenorphine 0.01 mg/kg (Ohtsuka Pharma Ltd.) was subcutaneously administered before and after surgery for pain relief. Two days after surgery, 0.3% acetic acid (AcOH, Wako Pure Chemical Corporation) in saline was injected into the bladder through the cannula and connected to the bladder for 30 min at an infusion rate of 4.0 mL/h. Alternatively, saline was injected into the normal saline with sham irradiation (NS + Sham) group using the same protocol.
(a) Time course of our experiment. (b) Schematics of our cystometry measurement system. Voiding urine volume and bladder pressure were measured simultaneously with continuous saline infusion through cannula. These measurements were performed under free moving.
Continuous cystometry
Schematics of our cystometry measurement system are shown in Fig 1B. Three days after surgery, bladder pressure was measured continuously using a transducer with an amplifier (ML117, ADInstruments, Ltd.) and recorded using an A/D converter (PowerLab system, ADInstruments, Ltd.) by transducing the cannula connected to the bladder. Voiding urine volume was measured continuously using a weighing meter under the cage. These measurements were performed with the animal freely mobile and simultaneously with continuous saline infusion at 3.0 mL/h and a constant speed through a T-shaped stopcock connected to the cannula.
Three groups were established—the NS+Sham group (saline infusion and sham irradiation, n = 3), the AcOH with sham irradiation (AcOH+Sham) group (AcOH infusion and sham irradiation, n = 8), and AcOH with laser irradiation (AcOH+Laser) group (AcOH infusion and laser irradiation, n = 8). To evaluate the effect of the laser with an appropriate evaluation range between the NS+Sham and AcOH groups, rats that had voiding intervals less than 10 min before laser irradiation were selected and enrolled uniformly in the AcOH+Sham group and AcOH+Laser group. Among a total of 38 animals, 19 were designated for evaluation and the remaining 19 were held in reserve. Exclusion criteria led to the removal of 15 rats from the evaluation group: 10 were excluded due to voiding intervals exceeding the standard 10-min threshold, 4 were excluded owing to tube breakage during cystometry procedures, and 1 was excluded due to overflow incontinence that precluded evaluation during cystometry measurements. 4 rats not enrolled in any group were euthanized under 2% isoflurane anesthesia. Cystometry was performed continuously for 60 min before and 120 min after laser irradiation. Residual urine was extracted from all the rats enrolled in the groups after cystometric measurement.
Laser irradiation
The laser conditions were set based on a previous report [28]. An 830 nm laser diode (Sheep, Unitac Inc.) was used as the light source. The irradiation parameter settings were 1 W average output, 10 W peak output, 180 s duration per each side (total: 360 s), 180 J energy per each side (total: 360 J), 1.5 cm2 beam area, 667 mW/cm2 average power density, 120 J/cm2 energy density per each side (total: 240 J/cm2), 10% pulse duty cycle, 20 ms pulse width, and 5 Hz frequency. Laser irradiation was applied to the skin on both sides of the L6 lumbosacral intervertebral foramen. The rats in the AcOH+Laser group were kept awake and retained during laser irradiation. Rats in the NS+Sham and AcOH + Sham groups were otherwise identically managed to the rats in the AcOH+Laser group, except for laser irradiation. The hair around the irradiated area of the skin was removed before laser irradiation in all groups.
Data analysis
Voiding intervals, urine volume, basal bladder pressure, and voiding bladder pressure were analyzed using a cystometry chart for each voiding, and the mean value was calculated for each rat, both before and after laser irradiation. Only data from 40 min before laser irradiation and from 30 to 120 min after laser irradiation were used to remove noise on the bladder pressure chart induced by intense body motion associated with the stress of retaining and holding the rat.
Prism v8.4.3 (Graph Pad Software Incorporated, San Diego, CA, USA) was used for the statistical analysis. Data are presented as the mean +/- standard error of the mean (S.E). For statistical analyses, we performed a one-way analysis of variance (ANOVA) followed by Bonferroni’s post-hoc comparisons tests or a two-way ANOVA followed by Bonferroni’s post-hoc comparisons tests; p < 0.05 was considered significant.
Results
Typical cystometry charts for the NS+Sham, AcOH+Sham and AcOH+Laser groups are shown in Fig 2, and the voiding interval and volume for each group are shown in Fig 3. Prior to sham or laser irradiation (pre), the voiding interval significantly decreased in the AcOH+Sham (417.9 +/- 51.2 s, p < 0.0001) and AcOH+Laser (408.0 +/- 54.3 s, p < 0.0001) groups, which received a 0.3% AcOH injection, compared to the NS+Sham group (1536.4 +/- 117.9 s) (Fig 3A). The voiding volume also significantly decreased in the AcOH+Sham (0.388 +/- 0.063 g, p = 0.0002) and AcOH+Laser (0.345 +/- 0.050 g, p = 0.0001) groups, compared to the NS+Sham group (1.093 +/- 0.205 g) (Fig 3B). There was no significant difference between the AcOH+Sham and AcOH+Laser groups in both of the voiding interval and voiding volumes (Fig 3A and 3B). The reduction in the voiding interval and volume due to AcOH indicated that the symptoms of cystitis were induced.
Pre: Charts before laser irradiation, Post: Charts after laser irradiation; NS, normal saline; AcOH, acetic acid.
(a, b) Prior to sham or laser irradiation (Pre), the voiding interval and voiding volume significantly decreased in the AcOH+Sham and AcOH+Laser groups, which received a 0.3% acetic acid instillation, compared to the NS+Sham group. There was no significant difference between the AcOH+Sham and AcOH+Laser groups. (c, d) Changes after sham or laser irradiation (post), expressed as a percentage relative to the pre-values. There were no significant changes in the voiding interval and voiding volume in the NS+Sham and AcOH+Sham groups between pre and post. The AcOH+Laser group showed a significant increase in both voiding interval and voiding volume. Pre: Values before sham or laser irradiation, Post: Values after sham or laser irradiation. Values represent mean +/- S.E (n = 3 or 8); individual data points are shown; ***: p < 0.001 and ****: p < 0.0001 vs. NS+Sham group using one-way ANOVA, followed by Bonferroni’s multiple comparisons tests; ##: p < 0.01 and ###: p < 0.001 vs. Pre using two-way ANOVA followed by Bonferroni’s multiple comparisons tests; NS, normal saline; AcOH, acetic acid.
To evaluate the effects of sham or laser irradiation, the values before irradiation (pre) were set to 100%, and the values after irradiation (post) were calculated. The values before and after sham or laser irradiation were compared. There were no significant changes in the voiding intervals in the NS+Sham (76%) and AcOH+Sham (155%) groups between pre and post. The AcOH+Laser group showed a significant increase in voiding interval between pre- and post (217%; p = 0.0002). There were also no significant changes in the voiding volume in the NS+Sham (86%) and AcOH+Sham (134%) groups between pre and post. The AcOH+Laser group showed a significant increase in voiding volume between pre and post (192%; p = 0.0012).
To evaluate the effects of the laser on voiding function, basal pressure, intravesical pressure, and residual urine volume were evaluated (Fig 4). At pre irradiation, no difference in basal pressure was observed among the NS+Sham (8.2 +/- 0.6 mmHg), AcOH+Sham (9.8 +/- 1.3 mmHg), and AcOH+Laser groups (10.8 +/- 1.1 mmHg) (Fig 4B). There was also no difference in intravesical pressure among the NS+Sham (44.4 +/- 6.5 mmHg), AcOH+Sham (40.6 +/- 5.7 mmHg), and AcOH+Laser groups (47.9 +/- 3.7 mmHg) (Fig 4B). Between the pre- and post-irradiation, there were no significant changes in basal pressure among the NS+Sham (108%), AcOH+Sham (88%), and AcOH+Laser groups (87%) (Fig 4C). There were also no significant changes in intravesical pressure among the NS+Sham (103%), AcOH+Sham (90%), and AcOH+Laser groups (100%) (Fig 4D). Residual urine volumes in the NS+Sham, AcOH+Sham, and AcOH+Laser group were 0.07 +/- 0.03 mL, 0.08 +/- 0.02 mL, and 0.10 +/- 0.02 mL, respectively (Fig 4E).
(a, b) Prior to sham or laser irradiation (Pre), there were no significant differences in basal pressure and intravesical pressure among the NS+Sham, AcOH+Sham, and AcOH+Laser groups. (c, d) Changes after sham or laser irradiation (Post), expressed as a percentage relative to the pre-values. There were no significant changes in any of the groups between Pre and Post. (e) Residual urine volume. There were no significant differences among any of the groups. Pre: Values before sham or laser irradiation, Post: Values after sham or laser irradiation. Values represent mean +/- S.E (n = 3 or 8); individual data points are shown; one-way ANOVA followed by Bonferroni’s multiple comparisons tests (a, b, e) or two-way ANOVA followed by Bonferroni’s multiple comparisons tests (c, d) were used; NS, normal saline; AcOH, acetic acid.
Discussion
Our study showed that urinary storage dysfunction was improved by laser irradiation without impairing the voiding function. Ito et al. reported that 830 nm laser diode irradiation suppressed bladder hyperactivity associated with the hypersensitivity of afferent nerves in a rat cystitis model induced by AcOH and PGE2 [28]. In their study, in rats with cystitis restrained in Bollman cages, the voiding interval measured by cystometry was prolonged after laser irradiation, corresponding to diminished bladder hyperactivity. These findings were consistent with our results. In our study, we compared three groups, the NS+Sham group (fistula preparation and saline infusion), AcOH+Sham group (fistula preparation and AcOH infusion), and AcOH+Laser group (fistula preparation, AcOH infusion, and laser irradiation), to remove any bias related to a change in the voiding interval due to long-term cystometry. In addition, cystometry was conducted with the animals freely mobile to remove any effects that might shorten the voiding interval due to restraint stress of restraint [29]. These methodologies contribute to increasing the reliability of experiments. Moreover, we observed an increase in voiding volume in the AcOH+Laser group, thereby elucidating the role of the laser in enhancing urinary storage dysfunction. Furthermore, there were no significant changes in basal or intravesical pressure following laser irradiation, and no alteration in residual urine volume occurred, indicating that voiding function was preserved. These findings indicate that PBM is an effective and safe treatment option for patients with cystitis.
In addition, laser irradiation did not affect bladder contraction during the voiding phase, despite improving bladder hyperactivity during the storage phase. In Ito’s study [28], laser irradiation did not alter the maximum intravesical pressure, although it prolonged voiding intervals in a rat cystitis model. This finding also supports our results, implying that laser irradiation may improve urine storage without the loss of voiding function. We consider that the selective control of the storage dysfunction resulting from the laser effect of 830 nm laser diode irradiation was due to the selective inhibition of afferent C and A delta fibers, but not efferent B fibers. The L6 lumbosacral nerve that projects to the bladder contains various nerve fibers, among which C and A-delta fibers transmit the sensation of the bladder to the center during the urinary storage period and efferent B fibers control bladder contraction during the voiding phase [25–27]. In a study by Ito et al., electrophysiological measurements of the L6 dorsal root ganglion activity showed that sensory nerve activity was suppressed by laser [28]. According to other electrophysiological studies, Tsuchiya et al. reported that 830 nm laser irradiation diminished the slow component of axonal volleys to dorsal roots from the saphenous nerve in rats, but did not affect the fast component of axial fibers [13]. They also reported that 830 nm laser irradiation depressed neuronal responses to nociceptive stimuli but did not alter the responses elicited by brush stimulation [14]. Other previous studies, which examined the effects of lasers on the firing frequency in the rat spinal dorsal horns evoked by mechanical stimulation, suggested that lasers did not affect the activity of A-beta fibers, but selectively inhibit the activity of C and A-delta fibers [15–17]. These results indicate that 830 nm laser irradiation selectively suppresses afferent C and A-delta fiber activity in our rat cystitis model. Selective inhibition of afferent C fand A-delta fibers by laser normalizes AcOH-induced hyperactivation of the micturition reflex, which may improve storage dysfunction. In contrast, bladder contraction during the voiding phase is controlled by efferent B-fibers, which have a relatively high conduction velocity [26]. Laser irradiation did not change the basal or intravesical pressure (Fig 4C and 4D), suggesting that the laser did not affect the activity of efferent B fibers. This may explain why laser irradiation did not affect bladder contraction during the voiding phase despite improving bladder hyperactivity during the storage phase.
The 830-nm laser was used to percutaneously irradiate the L6 lumbosacral intervertebral foramen at a power density of 667 mW/cm2 and an energy density of 120 J/cm2. In our previous report [30], the light penetration of the 830 nm laser used in this study was determined in the lumbosacral nerves of rats. We obtained a correlation between the depth of the nerves from the skin surface and the power density measured by implanting photodiodes near the lumbosacral nerves in rats. Laser power density and fluence at lumbosacral nerves were calculated as 23.2 mW/cm2 and 4.2 J/cm2 for these experimental conditions, respectively. According to the review by Huang, PBM effects appear to be obtained in the dose range of around 0.01–10 J/cm2 [2]. These findings confirm that a sufficient laser dose reached the lumbosacral nerves.
This study had several limitations. First, the mechanism underlying the selective inhibitory effect of PBM on nerve fibers remains unknown. This study suggests that PBM may have selectively suppressed A-delta and C fibers in a rat model of cystitis induced by AcOH. Future studies focusing on molecules specific to A-delta and C fibers may allow us to investigate the molecular mechanisms of PBM. Second, the dependence of the laser conditions on efficacy is unknown. A previous study reported that 808 nm PBM of L6 dorsal root ganglion with average power of 18–460 mW and energy of 10.8–276 J improved visceral hyperalgesia induced by restraint stress [31]. Although the animal model used in this study and the previous study differ, it is possible that similar mechanisms of action of PBM may have occurred. Therefore, it is likely that there are more effective treatment conditions for the cystitis model as well. Wavelength, power, and energy may have optimal therapeutic effects. Third, although a single irradiation was performed in this study, the persistence of the effect over 2 h is unknown, as is the accumulation of the effects of multiple irradiations. In pain treatment, the accumulation and persistence of effects are observed with multiple laser irradiations [7]. Assuming that the treatment mechanism suppresses the neural activity of A-delta and C-fibers as in the case of pain treatment, the effect may accumulate in the case of urinary symptoms as in the case of pain treatment. In the evaluation using cystitis model rats, the cystometry method used in this study is difficult to evaluate over multiple days. It may be possible to evaluate the effects of multiple irradiations using an evaluation method that allows spontaneous urination to be performed without creating a bladder fistula or saline infusion.
Conclusions
In this study, we investigated the effect of PBM on storage dysfunction and voiding function in rats with AcOH-induced cystitis subjected to transcutaneous laser irradiation of the lumbosacral nerves. Laser irradiation resulted in a significant increase in voiding interval and voiding volume, suggesting that bladder hyperactivity during the storage phase was improved by laser irradiation. Laser irradiation did not affect bladder contraction during the voiding phase. These results indicate that laser irradiation improves urinary storage dysfunction without the loss of voiding function. PBM may improve lower urinary tract dysfunction associated with detrusor overactivity.
Acknowledgments
We would like to express our gratitude to Ms. Emi Morita (Mediford Corporation) for her cooperation in the experiments.
Disclosure
Animal studies
All experimental procedures were conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals (Teijin Pharma Ltd.), and each experimental protocol was approved by the Committee for Animal Experiments of the Teijin Institute for Biomedical Research (approved project number: B16-042). Every effort was made to minimize suffering and the number of rats used.
References
- 1. Kingsley DJ, Demchak T., Mathis R. Low-level laser therapy as a treatment for chronic pain. Frontiers in Physiology. 2014; 5: 306.
- 2. Huang YY, Chen AC, Carroll JD, Hamblin MR. Biphasic dose response in low level light therapy. Dose Response. 2009; 7: 358–383. pmid:20011653
- 3. Oliveira S, Andrade R, Valente C, et al. Effectiveness of Photobiomodulation in Reducing Pain and Disability in Patients with Knee Osteoarthritis: A Systematic Review with Meta-Analysis. Phys Ther. 2024 May 22:pzae073. pmid:38775202
- 4. Tripodi N., Feehan J., Husaric M., Sidiroglou F., & Apostolopoulos V. The effect of low-level red and near-infrared photobiomodulation on pain and function in tendinopathy: a systematic review and meta-analysis of randomized control trials. BMC sports science, medicine & rehabilitation, 2021; 13(1), 91. pmid:34391447
- 5. Seyyedi SA, Taram S, Heydari M, Valizadeh R. Efficacy of low-level laser therapy in oral mucosal surgical wound healing: a systematic review and meta-analysis. Explor Med. 2022; 3: 451–60.
- 6. Huang Z, Ma J, Chen J, Shen B, Pei F, Kraus VB. The effectiveness of low-level laser therapy for nonspecific chronic low back pain: a systematic review and meta-analysis. Arthritis Res Ther. 2015; 17: 360. pmid:26667480
- 7. Chow RT, Johnson MI, Lopes-Martins RA, Bjordal JM. Efficacy of low-level laser therapy in the management of neck pain: a systematic review and meta-analysis of randomised placebo or active-treatment controlled trials. Lancet. 2009 5;374(9705):1897–908." pmid:19913903
- 8. Vanin AA, Verhagen E, Barboza SD, Costa LOP, Leal-Junior ECP. Photobiomodulation therapy for the improvement of muscular performance and reduction of muscular fatigue associated with exercise in healthy people: a systematic review and meta-analysis. Lasers Med Sci. 2018;33(1):181–214. pmid:29090398
- 9. Ma Y, Yang M, Chen X, Qu W, Qu X, He P. The effectiveness of photobiomodulation therapy on inferior alveolar nerve injury: A systematic review and META-analysis. PLoS One. 2023;18(8):e0287833. pmid:37561792
- 10. Da-young A., Seung-ho S. The Effect of Laser Therapy for Stroke Patients: A Systematic Review and Meta-analysis, The Journal of Korean Medicine 2024; 45(1): 44–63.
- 11. Jimbo K, Noda K, Suzuki K, Yoda K. Suppressive effects of low-power laser irradiation on bradykinin evoked action potentials in cultured murine dorsal root ganglion cells. Neurosci Lett. 1998; 240(2): 93–96. pmid:9486480
- 12. Chow R, Armati P, Laakso EL, Bjordal JM, Baxter GD. Inhibitory effects of laser irradiation on peripheral mammalian nerves and relevance to analgesic effects: a systematic review. Photomed Laser Surg. 2011; 29(6): 365–381. pmid:21456946
- 13. Tsuchiya K, Kawatani M, Takeshige C, Sato T, Matsumoto J. Diode laser irradiation selectively diminishes slow component of axonal volleys to dorsal roots from the saphenous nerve in the rat. Neuroscience letters. 1993; 161(1): 65–68. pmid:8255549
- 14. Tsuchiya K, Kawatani M, Takeshige C, Matsumoto J. Laser irradiation abates neuronal responses to nociceptive stimulation of rat-paw skin. Brain Res Bull. 1994; 34(4): 369–374. pmid:8082027
- 15. Uta D, Ishibashi N, Konnno T, et al. Near-Infrared Photobiomodulation of the Peripheral Nerve Inhibits the Neuronal Firing in a Rat Spinal Dorsal Horn Evoked by Mechanical Stimulation, Int. J. Mol. Sci. 2023; 24(3): 2352. pmid:36768673
- 16. Uta D, Ishibashi N, Kawase Y, Tao S, Sawahata M, Kume T. Relationship between Laser Intensity at the Peripheral Nerve and Inhibitory Effect of Percutaneous Photobiomodulation on Neuronal Firing in a Rat Spinal Dorsal Horn. J. Clin. Med. 2023; 12(15):5126. pmid:37568529
- 17. Uta D, Ishibashi N, Tao S, Sawahata M, Kume T. Photobiomodulation inhibits neuronal firing in the superficial but not deep layer of a rat spinal dorsal horn. Biochem Biophys Res Commun. 2024;710:149873. pmid:38583230
- 18. Andersson KE. Detrusor myocyte activity and afferent signaling. Neurourol Urodyn. 2010; 29: 97–106. pmid:20025035
- 19. Birder L, de Groat W, Mills I, Morrison J, Thor K, Drake M. Neural control of the lower urinary tract: peripheral and spinal mechanisms. Neurourol Urodyn. 2010; 29: 128–139. pmid:20025024
- 20. Zhang X, Igawa Y, Ishizuka O, et al. Effects of resiniferatosxin desensitization of capsaicin-sensitive afferents on detrusor over-activity induced by intravesical capsaicin, acetic acid or ATP in conscious rats. Naunyn Schmiedebergs Arch Pharmacol. 2003; 367: 473–479.
- 21. Ikeda M, Kawatani M, Maruyama T, Ishihama H. Prostaglandin facilitates afferent nerve activity via EP1 recetors during urinary bladder inflammation in rats. Biomed Res. 2006; 27: 49–54.
- 22. Yoshimura N, de Groat WC. Neural control of the lower urinary tract. Int J Urol. 1997; 4: 111–125. pmid:9179682
- 23. Shinozaki S, Saito M, Kawatani M. Loxoptrotein inhibits facilitated micturition reflex induced by acetic acid urinary bladder infusion of the rats. Biomed Res. 2005; 26: 29–33.
- 24. Cheng CL, Ma CP, de Groat WC. Effects of capsaicin on micturition and associated reflexes in rats. Am J Physiol. 1993; 265: 132–138. pmid:8342677
- 25.
Patterson PH, Reflex regulation of movement and posture. In Ruch T.C. et al.(Editors), Neurophysiology. Philadelphia: W.B. Saunders Company; 1960. Ch. 6, pp.167–198.
- 26. Yoshimura N, Chancellor MB. Neurophysiology of lower urinary tract function and dysfunction. Rev Urol. 2003;5 Suppl 8(Suppl 8):S3–S10. pmid:16985987
- 27. de Groat WC, Yoshimura N. Afferent nerve regulation of bladder function in health and disease. Handb Exp Pharmacol. 2009;(194):91–138. pmid:19655106
- 28. Ito T, Ishikawa T, Matsumoto-Miyai K, Kawatani M. Pulse diode laser irradiation (830 nm) of lumbosacral spinal roots diminished hyperreflexia-induced by acetic acid or prostaglandin E2 infusion in rat urinary bladder. LUTS. 2011; 3: 69–75. pmid:26676389
- 29. Fraser MO, Smith PP, Sullivan MP, et al. Best practices for cystometric evaluation of lower urinary tract function in muriform rodents. Neurourol Urodyn. 2020;39(6):1868–1884. pmid:32511810
- 30. Ishibashi N, Shimoyama H, Kawase Y, et al. Measurement of light penetration of near-infrared laser at the lumbosacral nerves in rats. Proc. SPIE 10477, Mechanisms of Photobiomodulation Therapy XIII. 2018; 1047704 (8 February 2018).
- 31. Ishibashi N, Nanjo T, Tao S. Photobiomodulation improves acute restraint stress-induced visceral hyperalgesia in rats. Lasers Med Sci. 2024; 39, 143. pmid:38806837