Abstract
Background & aims: Diabetic peripheral neuropathy (DPN) accounts for most common complications of T2DM. Painful DPN is associated with functional limitation & poor quality of life. Therefore, objective of the study is to find the effect of low level laser therapy on painful diabetic peripheral neuropathy (DPN) in type 2 diabetes mellitus (T2DM)
Materials & methods: The study design is pre-post observational design. After obtaining ethical clearance and informed consent, 19 T2DM subjects were screened and confirmed for peripheral neuropathy in an outpatient setting with biochemical parameter, pain scale and Michigan Neuropathy Screening Instrument (MNSI). Low Level Laser therapy was irradiated through scanning mode with dosage of 3.1J/cm2 on the plantar and dorsum of the foot and 3.4j/cm2 with contact method for 10days and all subjects were reassessed at the end of the 10 day. Descriptive statistics and paired′ test was used to analyze the pre-post finding within the group. Level of significance was set at p<0.05
Results: The result analysis showed significant reduction in Pain using VAS scale (6.47 ± 0.84 to 1.21 ± 0.78 (p<0.001), MNSI (5.52 ± 1.26 to 2.71 ± 0.97 (reduction in Vibration perception threshold (32.68 ± 6.08 to 24.84 ± 4.29 (<0.001) and a significant increase in the temperature from baseline to post intervention (30.01 ± 2.11 to 31.75 ± 1.03 (p<0. 001).
Conclusion: In the present study, Low level laser therapy was found to be effective in type 2 DM with peripheral neuropathy.
Keywords: Type 2 diabetes mellitus, Peripheral Neuropathy, Pain, Low Level Laser Therapy
Introduction
The prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasing worldwide. It has been associated with many micro-vascular and macro-vascular complications. 1) Among all the complications, peripheral neuropathy is considered to be the most common. 2) It is estimated that the prevalence of peripheral neuropathy in T2DM patients is approximately 25–50% in developing countries. 3) Diabetic peripheral neuropathy (DPN) accounts for more hospitalization than all the other complications of T2DM. Painful DPN is associated with functional impairment & poor quality of life. 4, 5)
Painful DPN is a result of injury to the Vasa nervorum, axons and atrophy of the axons leading to tissue damage. 6) All nerve fibres may be injured, but small myelinated and unmyelinated fibres that transmit pain and temperature are most affected. 6) In association with injury to the nerves, reduced microcirculation is responsible for the loss of protective sensation and atrophy of intrinsic foot muscles which later leads to development of foot complications like callus, ulcers, and infections of skin and bone in T2DM subjects with long duration of diabetes mellitus. 7) In many subjects with diabetic neuropathy, pain develops as a symptom localized to the lower extremities, primarily the soles and toes. 8)
Current therapy for painful DPN is aiming to symptomatic relief through various drug administrations. These drugs are effective, but often associated with systemic side effects and do not retard the advancement of the underlying neuropathy. 9) Other than pharmacological treatment, non-pharmacological management have also been used, including acupuncture 10), infrared therapy 11), and various electrotherapies, including transcutaneous electrical nerve stimulation (TENS) 12), and spinal cord electro stimulation. 13) The efficacy of most conservative treatment options for painful DPN is still needs to be investigated. Among the electrotherapy modalities, low-level laser therapy has been used to manage nerve injuries and other pathologies of the nerve because it hold the potential to induce a biostimulational effect on the nervous system. 14 – 16) In addition, low-level laser therapy has also been used in the management of diabetic complications such as foot ulcers. 17) Even though low-level laser therapy is found to be very effective in nerve regeneration, there is a dearth of literature on effect of low-level laser therapy on painful DPN in T2DM population. Therefore the objective of the present study is to evaluate the effect of low-level laser therapy on Type 2 DM subjects with painful DPN.
Materials & methods
After obtaining Institutional Ethical Committee (IEC) clearance and informed written consent, 19 T2DM subjects on oral hypoglycaemic agents were recruited based on inclusion and exclusion criteria. The neuropathy evaluation was performed using Michigan Neuropathy Screening Instrument (MNSI), Vibration Perception Threshold (VPT) using Biothesiometer. Pain was assessed using Visual Analogue Scale (VAS), temperature was assessed using Infrared Thermal Imaging. Subjects with malignancy, thyroid disease, other neurological conditions, pregnancy, were excluded from the study.
Following detailed base line evaluation, all 19 subjects were treated with two separate low level laser therapy equipment. The EC laser wave length of 632.8 nm with dosage of 3.1J/cm2 and Thor Laser wave length of 660nm & 850 nm with dosage of 3.4J/cm2 and power density of 50–150 mW/cm2. The EC laser was treated with scanning mode with duration of nine minute on the plantar and dorsum of foot (Figure-1) and Thor Laser probe was used with contact method over popliteal fossa (Figure-2) and over the neck of fibula for 10 days and all subjects were reassessed at the end of the 10th day by using following outcome measures, VAS, MNSI, VPT and temperature by infrared thermal imaging. All the subjects completed laser treatment without any adverse reaction. Data was analyzed using SPSS package version 16. Descriptive statistics and paired ‘t’ test was performed to analyze the pre-post changes within the group. Level of significance was set at p<0.05.
Figure 1.
Scanning method of Laser application
Figure 2.
Laser with Probe method application
Result analysis
Nineteen T2DM subjects with mean age of 49.58 ± 6.89 years and DPN with mean duration of 7.84 ± 3.77 years. Table 1 shows the demographic characteristics of the T2DM subjects.
Table 1. Demographic characteristics of the subjects.
| Parameters | Mean±SD |
| Age (years) | 49.58±6.89 |
| Gender | Male-12 & Female-07 |
| BMI (Kg/m2) | 24.94±2.03 |
| Fasting Blood Sugar (mg/dl). | 184.47±30.08 |
| Post Prandial Blood Sugar (mg/dl) | 242.74±60.06 |
| HbAc (%) | 9.08±1.09 |
| Duration of T2 DM (years) | 13.58±5.08 |
| Duration of Peripheral Neuropathy (years) | 7.84±3.77 |
The result analysis showed significant reduction in Pain using VAS scale (6.47 ± 0.84 to 1.21 ± 0.78 (p<0.001), MNSI (5.52 ± 1.26 to 2.71 ± 0.97 (<0.001). In addition we observed significant reduction in Vibration perception threshold (32.68 ± 6.08 to 24.84 ± 4.29 (<0.001) and a significant increase in the temperature from baseline to post intervention (30.01 ± 2.11 to 31.75 ± 1.03 (p<0. 001). (Table 2)
Table 2. Pre-Post Mean changes in outcome measures after low level laser therapy in T2DM with peripheral Neuropathy.
| Outcome measures | Base Line | 10th day | 95% confidence Interval | P | |
|---|---|---|---|---|---|
| Mean ±SD | Mean ±SD | Lower | Upper | ||
| Pain | 6.47±0.84 | 1.21±0.78 | −4.75 | 5.76 | <0.0001 |
| MNSI | 5.52±1.26 | 2.71±0,97 | −1.90 | 3.72 | <0.0001 |
| VPT | 32.68±6.08 | 24.84±4.29 | −6.05 | 9.62 | <0.0001 |
| Temperature | 30.01±2.11 | 31.75±1.03 | −0.84 | 4.11 | <0.0001 |
Discussion
Painful DPN is one of the common complications in subjects with T2DM. From a pathophysiological standpoint, DPN is derived not only from injury to peripheral nerves but most commonly of micro vascular origin. 18), 19) So the treatment of DPN pain could be directed to improve microcirculation, enhance regeneration of nerve injury and reduce pain.
In the present study, we used low level laser therapy to determine its effect on painful Diabetic Peripheral Neuropathy (DPN). The results showed significant reduction in the pain (Table 2). The possible explanatory factor for reduction in pain could be due to increased microcirculation to the periphery. 20) The possible mechanism is that low-level laser therapy stimulates the release of cytokines and growth factors into the circulation which are responsible for the vasodilatation of the vessels and formation of new capillaries. A study conducted by Funk et al. documented that exposure to He-Ne laser stimulates the release of cytokines such as IL-1α, IL-2, IFN-γ and TNF-α which plays a major role in cell signalling. 21)
Other possible reason for reduction in pain can also be due to increased ATP production by mitochondria and increased cellular oxygen consumption by nerve regeneration. Low-level laser therapy increases microcirculation to the periphery and to understand this mechanism, in the present study we used Infrared thermal camera to record the foot temperature, as temperature represents the state of blood circulation where reduced temperature is considered as diminished blood supply to the periphery and increased temperature represents increased blood circulation to the periphery. In the present study, with laser irradiation, we found an increase in temperature following laser therapy. Our result were supported by the previous finding on improvement of microcirculation at the irradiation site. 22), 23)
In addition to decrease in pain and improved micro circulation, we observed that there is mean decrease in Michigan Neuropathy Screening Instrument (MNSI) and vibration threshold in all subjects. (Table 2) However, study conducted by Arnall et al 24) evaluated the vibration perception threshold (VPT) and found no improvement after laser irradiation, but in the present study we found decrease in the vibration perception threshold following laser irradiation. The possible reason could be due to increased microcirculation and release of cell signaling proteins like cytokines.
Conclusion
In the present study, we found that low-level laser therapy is effective in reducing pain in T2DM with peripheral neuropathy.
Limitation of the study
Present study is a pre-post experimental study with no control group.
Table 3. Demographic & Clinical characteristics of Participants.
| Case | Gender | Age (Years) | BMI (kg/m2) | Glycated Hb (%) | Duration of Diabetes (Years) | Peripheral Neuropathy (Years) |
|---|---|---|---|---|---|---|
| Case 1 | Male | 45 | 24.5 | 11.2 | 13 | 7 |
| Case 2 | Female | 57 | 24.7 | 9.3 | 8 | 4 |
| Case 3 | Male | 42 | 26 | 7.1 | 5 | 2 |
| Case 4 | Female | 53 | 22.8 | 12.3 | 15 | 9 |
| Case 5 | Male | 42 | 22.7 | 10.4 | 14 | 10 |
| Case 6 | Male | 55 | 27.6 | 11.5 | 15 | 7 |
| Case 7 | Female | 58 | 26.8 | 10.2 | 18 | 12 |
| Case 8 | Male | 44 | 25.8 | 9.4 | 19 | 14 |
| Case 9 | Male | 55 | 27.5 | 7.4 | 9 | 5 |
| Case 10 | Male | 49 | 24.5 | 10.6 | 15 | 9 |
| Case 11 | Female | 41 | 27.6 | 8.3 | 18 | 13 |
| Case 12 | Male | 57 | 26.8 | 11.2 | 26 | 15 |
| Case 13 | Male | 44 | 25.8 | 9.5 | 13 | 9 |
| Case 14 | Female | 61 | 20.1 | 8.6 | 15 | 6 |
| Case 15 | Female | 57 | 24.7 | 9.3 | 8 | 4 |
| Case 16 | Male | 42 | 26 | 7.1 | 5 | 2 |
| Case 17 | Female | 53 | 22.8 | 12.3 | 15 | 7 |
| Case 18 | Male | 45 | 24.5 | 11.2 | 13 | 6 |
| Case 19 | Male | 42 | 22.7 | 10.4 | 14 | 8 |
Table 4: Pre and post changes in outcome measures after low level laser therapy T2DM with Peripheral neuropathy.
| Case | FBS pre (mg/dl) | FBS post (mg/dl) | PPBS pre (mg/dl) | PPBS post (mg/dl) | VAS pre | VAS post | MNSI pre | MNSI post | VPT pre | VPT post | Temperature pre | Temperature post |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case 1 | 147 | 128 | 155 | 158 | 7 | 2 | 7 | 4 | 45 | 26 | 28.1 | 31.4 |
| Case 2 | 260 | 191 | 197 | 152 | 6 | 1 | 7.5 | 3 | 38 | 29 | 31.2 | 31.3 |
| Case 3 | 131 | 136 | 215 | 196 | 6 | 0 | 5 | 4 | 28 | 22 | 32.1 | 31.2 |
| Case 4 | 185 | 136 | 153 | 162 | 7 | 1 | 6 | 2 | 31 | 21 | 26.3 | 30.5 |
| Case 5 | 191 | 152 | 241 | 198 | 5 | 2 | 4 | 2.5 | 33 | 30 | 27.3 | 31.5 |
| Case 6 | 261 | 179 | 284 | 219 | 8 | 2 | 3.5 | 3.5 | 32 | 24 | 30.2 | 31.8 |
| Case 7 | 155 | 121 | 238 | 198 | 7 | 2 | 6.5 | 3 | 35 | 26 | 31.4 | 32.2 |
| Case 8 | 321 | 141 | 368 | 198 | 6 | 1 | 7 | 2 | 43 | 32 | 31.12 | 33.2 |
| Case 9 | 138 | 109 | 120 | 141 | 8 | 2 | 6 | 2.5 | 26 | 19 | 28.3 | 33.2 |
| Case 10 | 198 | 138 | 210 | 191 | 6 | 1 | 5.5 | 2 | 42 | 33 | 30.2 | 31.7 |
| Case 11 | 203 | 198 | 314 | 262 | 7 | 2 | 4 | 4 | 26 | 21 | 33.4 | 32.5 |
| Case 12 | 141 | 256 | 214 | 312 | 6 | 0 | 7 | 0 | 35 | 23 | 31.21 | 32.8 |
| Case 13 | 210 | 198 | 300 | 231 | 7 | 1 | 5 | 2 | 32 | 24 | 26.3 | 29.4 |
| Case 14 | 252 | 291 | 529 | 324 | 6 | 2 | 6 | 2.5 | 29 | 25 | 31.34 | 33.2 |
| Case 15 | 109 | 139 | 213 | 242 | 7 | 0 | 5 | 2.5 | 25 | 18 | 33.2 | 31.2 |
| Case 16 | 103 | 98 | 173 | 169 | 6 | 1 | 5 | 3.5 | 24 | 21 | 30.2 | 32.4 |
| Case 17 | 226 | 218 | 332 | 242 | 5 | 2 | 6 | 2 | 33 | 25 | 28.3 | 31.3 |
| Case 18 | 112 | 109 | 193 | 157 | 7 | 1 | 6 | 3 | 35 | 30 | 31.1 | 32.2 |
| Case 19 | 162 | 125 | 163 | 155 | 6 | 0 | 3 | 3.5 | 29 | 23 | 29.1 | 30.3 |
[Acknowledgement]
This study was supported by Dr. TMA PAI Endowment Chair in Exercise Science & Health promotion, Manipal University, Manipal. Mr Shashi Kumar is the guarantor of this work and had full access to all the information in the field and assumes responsibility for the integrity of the information and accuracy of the data analysis.
References
- 1: Hile C, Veves A. Diabetic neuropathy and microcirculation. Curr Diab Rep. 2003; 3(6):446-51. [DOI] [PubMed] [Google Scholar]
- 2: Andrew J.M., Boulton: Management of Diabetic Peripheral Neuropathy. Clinical Diabetes 2005, 23:9-15. [Google Scholar]
- 3: Boulton AJ, Malik RA, Arezzo JC. Diabetic somatic neuropathies. Diabetes Care 2004, 27:1458-1486. [DOI] [PubMed] [Google Scholar]
- 4: Galer BS, Gianas A, Jensen MP. Painful diabetic polyneuropathy: epidemiology, pain description, and quality of life. Diabetes Res Clin Pract 2000, 47:123-128. [DOI] [PubMed] [Google Scholar]
- 5: Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care 2003, 26:1790-1795. [DOI] [PubMed] [Google Scholar]
- 6: Irina G. Obrosova. Diabetes and the peripheral nerve. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 2009;10: 931-940. [DOI] [PubMed] [Google Scholar]
- 7: Bharara M, Cobb JE, Claremont DJ. Thermography and thermo-metry in the assessment of diabetic neuropathic foot: a case for furthering the role of thermal techniques. Int J Low Extrem Wounds. 2006; 5(4):250-60. [DOI] [PubMed] [Google Scholar]
- 8: Abeer A, Yamany, Hayam M. Sayed. Effect of low level laser therapy on neurovascular function of diabetic peripheral neuropathy. Journal of Advanced Research, 2012; 3(1): 21-28. [Google Scholar]
- 9: Davies M, Brophy S, Williams R, Taylor A. The prevalence, severity and impact of painful diabetic peripheral neuropathy in type 2 diabetes. Diabetes Care 2006; 29(7):1518-22. [DOI] [PubMed] [Google Scholar]
- 10: De Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depression and diabetes complications: a meta-analysis. Psychosom Med 63:619-630, 2001. [DOI] [PubMed] [Google Scholar]
- 11: Francisco V Santos, Chiappa Gaspar R., Vieira Paulo J. C., Umpierra Daniel, Ribeiro Jorge P., Cipriano Gerson., Jr. Interferential electrical stimulation improves peripheral vasodilatation in healthy individuals. Braz J Phys Ther. 2013. May-Jun; 17(3):281-288. [DOI] [PubMed] [Google Scholar]
- 12: Dworkin RH, O'Connor AB, Backonja M, Farrar JT, Finnerup NB, Jensen TS, et al. Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007; 132(3):237-51. [DOI] [PubMed] [Google Scholar]
- 13: Slangen Rachel, Schaper Nicolaas C., Faber Catharina G., Joosten Elbert A., Dirksen Carmen D., van Dongen Robert T., Kessels Alfons G., van Kleef Maarten. Spinal Cord Stimulation and Pain Relief in Painful Diabetic Peripheral Neuropathy: A Prospective Two-Center Randomized Controlled Trial. Diabetes Care 2014;37:3016-3024. [DOI] [PubMed] [Google Scholar]
- 14: Leonard DR, Farooqi MH, Myers S. Restoration of sensation, reduced pain, and improved balance in subjects with diabetic peripheral neuropathy: a double-blind, randomized, placebo controlled study with monochromatic near-infrared treatment.\ Diabetes Care 2004;27(1):168-72. [DOI] [PubMed] [Google Scholar]
- 15: Zinman LH, Ngo M, Ng ET, Nwe KT, Gogov S, Bril V. Low intensity laser therapy for painful symptoms of diabetic sensorimotor polyneuropathy: a controlled trial. Diabetes Care 2004; 27(4):921-4. [DOI] [PubMed] [Google Scholar]
- 16: Hashni Javad T., Huang Ying-Ying, Osmani Bushra Z., Sharma Sulbha K., Naeser Margaret A., et al. Role of Low-Level Laser Therapy in Neurorehabilitation. 2010; 2(12 Suppl 2): S292-S305. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17: Anders JJ, Borke RC, Woolsey SK, Van de Merwe WP. Low power laser irradiation alters the rate of regeneration of the rat facial nerve. Lasers Surg Med 1993; 13(1):72-82. [DOI] [PubMed] [Google Scholar]
- 18: Barbosa RI, Marcolino AM, de Jesus Guirro RR, Mazzer N, Barbieri CH, de Cassia Registro Fonseca M. Comparative effects of wavelengths of low-power laser in regeneration of sciatic nerve in rats following crushing lesion. Lasers Med Sci 2010; 25(3):423-30. [DOI] [PubMed] [Google Scholar]
- 19: Kazemi Khoo N. Successful treatment of diabetic foot ulcers with low-level laser therapy. The Foot 2006; 16(4):184-7. [Google Scholar]
- 20: Gungormus M, Akyol UK. Effect of biostimulation on wound healing in diabetic rats. Photomed Laser Surg 2009;27(4):607-10. [DOI] [PubMed] [Google Scholar]
- 21: Funk J. O., Kruse A., Neustock P., Kirchner H. Helium - neon laser irradiation induces effects on cytokine production at the protein and the mRNA level. Exp. Dermatol 1993. 2;75-83. [DOI] [PubMed] [Google Scholar]
- 22: Bjordal JM, Couppe C, Chow RT, Tuner J, Ljunggren EA. A systematic review of low level laser therapy with location-specific doses for pain from chronic joint disorders. Aust J Physiother 2003; 49(2):107-16. [DOI] [PubMed] [Google Scholar]
- 23: Bjordal JM, Johnson MI, Iversen V, Aimbire F, Lopes Martins RA. Photoradiation in acute pain: a systematic review of possible mechanisms of action and clinical effects in randomized placebo controlled trials. Photomed Laser Surg 2006; 24(2):158-68. [DOI] [PubMed] [Google Scholar]
- 24: Arnall DA, Nelson AG, Lopez L, Sanz N, Iversen L, Sanz I, Stambaugh L, Arnall SB. The restorative effects of pulsed infrared light therapy on significant loss of peripheral protective sensation in patients with long-term type 1 and type 2 diabetes mellitus. Acta Diabetol 43:26-33, 2006. [DOI] [PubMed] [Google Scholar]