Another injection therapy that has proven useful is Perineural Injection Therapy (PIT). PIT is the injection of isotonic dextrose or mannitol close to superficial, subcutaneous nerves to restore normal function in nerves that cause chronic pain and degeneration. Treating with a combination of pro-lotherapy and perineural injection simultaneously addresses nerve, liga-ment, tendon, muscle, and joint sources of pain. There is another type of inflamma-tion that has been recognized, neuro-genic inflammation. This type of in-flammation is produced by special small sensory nerves that are pro-tein-producing (“peptidergic”). Neu-rogenic inflammation occurs when a nerve produces painful or damaging proteins. The receptor that is involved is TRPV-1 (transient receptor poten-tial vanilloid -Type 1) also known as the capsaicin receptor, which plays a central role in the development of allodynia and hyperalgesia in patients with chronic pain. xxii, xxiii Chronic neuropathic pain is asso-ciated with persistent upregulation of the TRPV1 ion channel. Studies sug-gest a potential nerve-specific or sensorineural mechanism for pain reduction following perineural injec-tion of isotonic 5% dextrose (D5W) xxv Dextrose acts at the level of the TRPV1 receptor. Mannitol, a metabolically inert sugar molecule that is structurally similar to dextrose, has been reported to reduce pain re-sulting from upregulation of TRPV1 ion channels in an RCT using a cap-saicin pain model. xxv TRPV-1 nerves are not only irri-tated when they have to penetrate fascia at the skin level, but also when they have to penetrate layers of fascia in other regions, such as fibro-osseus tunnels, or passages. Any of these areas can malfunction or be changed in such a way as to “touch” the TRPV -1 nerve. Perineural injections use 5% dex-trose water (D5W) as a fluid injection under pressure to purposely separate nerves from areas of suspected fascial compression, which are increasingly viewed as potential perpetuating fac-tors in recalcitrant neuropathic pain/ www.Cndoctor.ca PIT AND HOW IT WORKS complex regional pain. The mecha-nism of analgesia may be related to an indirect (allosteric) effect on the TRPV1 cation channel, and the injec-tion of D5W results in a release of the fascial compression of a suspected local neural compression. This ad-dresses chronic constriction injury which contributes to neuropathic pain and neural swelling. xxvi The judicious use of prolotherapy and perineural injections can be an important element of a comprehen-sive, holistic treatment plan to ad-dress structural and neural aspects of chronic pain. The proliferative prop-erties of hypertonic dextrose can fa-cilitate tissue repair via arachidonic acid pathways, leading to the resolu-tion of chronic ligamentous and tendonous pain. Perineural injection with isotonic dextrose or mannitol can address neuropathic pain that is a driver of chronic pain. The down-regulation of the TRPV-1 re-ceptor re-establishes neuronal func-tion and results in a return to normal innervation that improves pain and function. Both of these therapies are without the harms associated with medica-tion-based interventions such as long-term opioid use, corticosteroids, nonsteroidal and immunosuppressive therapies and surgical interventions by addressing the underlying pain pathology. vii Centeno, Christopher, MD, Elliott, James, MSPT, et. Al, “Fluor-oscopically Guided Cervical Prolotherapy for Instability with Blinded Pre and Post Radiographic Reading”, Pain Physician, 2005;8:67-72. viii Wilkinson, Harold, MD, PhD. ‘Injection Therapy for Enthe-sopathies Causing Axial Spine Pain and ‘The Failed Back Syn-drome:’ A Single Blinded, Randomized and Cross-Over Study”, Pain Physician, 2005;8:167-173. ix Mayo Clinic Health Letter, Volume 23, Number 4, April 2005 x Dagenais, Simon, DC, PhD., Haldeman, Scott, DC, MD, Wooley, J, DC, “Intraligamentous Injection of Sclerosing Solutions (Pro-lotherapy) for Spinal Pain: A Critical Review of the Literature”, The Spine Journal 5 (2005) 310-328. xi Rabago, David, MD, Best, Thomas, MD, et. al, A systematic Review of Prolotherapy for Chronic Musculoskeletal Pain”, Clin-ical Journal of Sports Medicine, Vol 15, Number 5, September 2005. xii Linetsky, Felix, MD., Miguel, R, MD, Saberski, L., MD, “Pain Management with Regenerative Injection Therapy (RIT), Pain Management, A Practical Guide for Clinicians, Sixth Edition, American Academy of Pain Management, CRC Press, 2002, pp. 381-402 xiii Linetsky, Felix, MD, Eek, B, MD, Derby, R, MD, Parris, C.V.W., MD, “Regenerative Injection Therapy”, Low Back Pain, Diagnosis and Treatment, Interventional Pain Management, ASIPP Pub-lishing, 2002, pp. 519-540.Chronic pain xiv Martins et al. Martins CA, Bertuzzi RT, Tisot RA, et al. Dextrose prolotherapy and corticosteroid injection into rat Achilles ten-don. Knee Surg Sports Traumatol Arthrosc 2012;20:1895-900. xv Oh S, Ettema AM, Zhao C, et al. Dextrose-induced subsynovial connective tissue fibrosis in the rabbit carpal tunnel: A potential model to study carpal tunnel syndrome? Hand (N Y). 2008;3(1):34-40. xvi Yoshii Y, Zhao C, Schmelzer JD, et al. The effects of hypertonic dextrose injection on connective tissue and nerve conduction through the rabbit carpal tunnel. Arch Phys Med Rehabil 2009;90:333-9 xvii Yoshii Y, Zhao C, Schmelzer JD, et al. Effects of hypertonic dextrose injections in the rabbit carpal tunnel. J Orthop Res 2011;29:1022-7 xviii Yoshii Y, Zhao C, Schmelzer JD, et al. Effects of multiple injections of hypertonic dextrose in the rabbit carpal tunnel: a potential model of carpal tunnel syndrome development. Hand (N Y) 2014;9:52-7 xix Maniquis-Smigel L, Reeves KD, Rosen JH, et al. Short term analgesic effects of 5% dextrose epidural injection for chronic low back pain. A randomized controlled trial. Anesth Pain Med. 2017;7(1):e42550. xx Maniquis-Smigel L, Reeves KD, Rosen JH, et al. Analgesic effect and potential cumulative benefit from caudal epidural D5W in consecutive participants with chronic low back and buttock/leg pain. Jnl Alt Compl Med. 2018 xxi Topol GA, Podesta LA, Reeves KD, et al. The chondrogenic effect of intra-articular hypertonic-dextrose (prolotherapy) in severe knee osteoarthritis. PMR. 2016;8(11):1072-1082. xxii Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and Molecular Mechanisms of Pain. Cell. 2009;139(2):267-284. xxiii Cui M, Gosu V, Basith S, et al. Polymodal Transient Receptor Potential Vanilloid Type 1 Nocisensor: Structure, Modulators, and Therapeutic Applications. Adv Protein Chem Struct Biol. 2016;104:81-125. xxiv Wu P, Diaz R, Borg-Stein J. Platelet-Rich Plasma. Phys Med Rehabil Clin N Am. 2016;27(4):825-853. xxv Bertrand H, Kyriazis M, Reeves KD, et al. Mannitol cream in the treatment of postherpetic neuralgia: Randomized, place-bo-controlled, crossover pilot study (Abs). Can Fam Physician. 2017;63(Suppl 1):S106. xxvi Lam SKH, Reeves KD, Chang AL. Transition from deep re-gional blocks toward deep nerve hydrodissection in the upper body and torso. Method description and results from a retro-spective chart review of the analgesic effect of 5% dextrose water as the primary hydrodissection injectate. Biomed Res Int 2017;7920438 (doi.org/10.1155/2017/7920438). REFERENCES i Woolf AD, Erwin J, March L. The need to address the burden of musculoskeletal conditions. Best Pract Res Clin Rheumatol. 2012 Apr;26(2):183-224. doi: 10.1016/j.berh.2012.03.005. PMID: 22794094. ii Fiona M. Blyth, Andrew M. Briggs, Carmen Huckel Schneider, Damian G. Hoy, and Lyn M. March 2019: The Global Burden of Musculoskeletal Pain—Where to From Here? American Journal of Public Health 109, 35_40, https:// doi.org/10.2105/AJPH.2018.304747 iii Frank C. The Pathophysiology of Ligaments. Chapter 2:11-18. In: Arendt EA. Orthopedic Knowledge Update: Sports Medicine 2, American Academy of Orthopedic Surgeons, 1999. iv Rodeo SA, Izawa K. Pathophysiology of Tendinous Tissue. Chapter 4: 29-36. In: Arendt EA. Orthopedic Knowledge Update: Sports Medicine 2, American Academy of Orthopedic Surgeons, 1999.Cyriax, J. Textbook of Orthopedic Medicine, Bailliere Tindall, London, 1982. v Topol, Gaston A,MD, Reeves, K. Dean, MD, Hassanein, K.M, PhD., “Efficacy of Dextrose Prolotherapy in Elite Male Kick-ing-Sport Athletes with Chronic Groin Pain”, Arch Phys Med Rehabil , Vol 86, April 2005. vi Ohberg, Lars, Alfredson, H, “Sclerosing Therapy in Chronic Achilles Tendon Insertional Pain—Results of a Pilot Study”, Knee Surg Sports Traumatol Arthrosc, (2003) 11:pp.339-343. March/April 2021 Chiropractic and Naturopathic Doctor 21
Chiropractic + Naturopathic Doctor March/April 2021: Page 21
