Postoperative Peripheral Nerve Stimulation for Management of Post-amputation Pain

Effects of Postoperative Percutaneous Peripheral Nerve Stimulation on Acute and Chronic Amputation Pain

Limb loss is frequently associated with postamputation pain that can be challenging to treat and often involves opioids. Advances in the field of neuromodulation has led to development of an intentionally reversible percutaneous peripheral nerve stimulation (PNS) system that has had promising results when treating chronic postamputation pain. PNS may offer sustained pain relief even after the treatment period has ended. Currently, there is no convincing evidence regarding the role of PNS in the acute postoperative period, which may be a critical time to control pain as those with higher pain appear to be at higher risk for developing persistent post-procedural pain. The investigators of this study aim to evaluate the feasibility and effects of PNS in the acute postoperative period and determine the feasibility of completing a randomized controlled treatment outcome study.

16 patients with new nontraumatic transfemoral or transtibial amputation will be enrolled in the study Having met inclusion criteria, the patients will be randomized to experimental or control groups Patients in the experimental group undergo placement of PNS leads within 7 days of amputation surgery Patients in both groups will be treated with standard pharmacologic and nonpharmacologic pain therapies and evaluated weekly for 8 weeks, then at 3, 6, and 12 months postamputation

Standard medical therapy and 30 to 60 days of peripheral nerve stimulation starting within 7 days after surgery

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their PLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their RLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their PLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their RLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their PLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate their RLP over the past 24 hours on a scale of "0"=no pain to "10"=worst pain they have ever experienced. A lower score is better. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

The number of subjects prescribed any opioid medication and any dose. Data from Weeks 1-4 and Weeks 5-8 were averaged to obtain a numerical score for these time points.

FIM mobility subscores were recorded by a physical therapist to measure the ability to walk, use a wheelchair, transfer to tub/shower, transfer to toilet, and mobility in bed, chair, and wheelchair. Scores range from "1" = subject requires total assistance for the task to "7" = complete independence. A higher score is better.

Using the Brief Pain Inventory-Short Form (BPI-SF) questionnaire, subjects were asked to rate how much pain has interfered with daily activities over the past 24 hours on a scale of "0" = no interference to "10" = completely interferes with activities. A lower score is better.

Self-report measure PGIC reflects a patient's belief about the efficacy of treatment. PGIC is a 7 point scale depicting a patient's rating of overall improvement. Patients rate their change as 1 = "very much improved," 2 = "much improved," 3 = "minimally improved," 4 = "no change," 5 = "minimally worse," 6 = "much worse," or 7 = "very much worse." A lower score is better.

Pain catastrophizing is the tendency to magnify the threat value of a pain stimulus and to feel helpless in the presence of pain. This is further characterized by the inability to prevent or inhibit pain-related thoughts surrounding a painful event. Pain catastrophizing affects how individuals experience pain. The PCS is a 13-item inventory of statements in which the subject is asked to rate the degree to which they agree, on a scale of "0" = not at all to "4" = all the time. The responses for each item are added for a total PCS score (range 0-52). A lower score is better.

The PDI is designed to measure the degree to which aspects of life are disrupted by chronic pain. The impact of pain on various aspects of life (e.g. family/home responsibilities, recreation, social activity, occupation, sexual behavior, self-care, and life-support activities) are recorded on a 10-point scale from "0" = no disability to "10" = worst disability. The sum of scores is recorded for a total PDI score (range 0-70). A lower score is better.

Hospital LOS was calculated from day of surgery to day of discharge from inpatient hospital ward to rehabilitation facility.

Inclusion Criteria: Nontraumatic transfemoral (above-the-knee) or transtibial (below-the-knee) amputation Presence of postamputation pain rated at least 4 or more Exclusion Criteria: Beck Depression Inventory score greater than 20 Systemic infection Immunocompromised or taking immunosuppressive medications Implanted electronic device Pregnancy Previous allergy to skin contact materials and/or anesthetic agent Altered mental status Inability to provide informed consent

Hanley MA, Jensen MP, Smith DG, Ehde DM, Edwards WT, Robinson LR. Preamputation pain and acute pain predict chronic pain after lower extremity amputation. J Pain. 2007 Feb;8(2):102-9. doi: 10.1016/j.jpain.2006.06.004. Epub 2006 Sep 1.

Karanikolas M, Aretha D, Tsolakis I, Monantera G, Kiekkas P, Papadoulas S, Swarm RA, Filos KS. Optimized perioperative analgesia reduces chronic phantom limb pain intensity, prevalence, and frequency: a prospective, randomized, clinical trial. Anesthesiology. 2011 May;114(5):1144-54. doi: 10.1097/ALN.0b013e31820fc7d2.

Kent ML, Hsia HJ, Van de Ven TJ, Buchheit TE. Perioperative Pain Management Strategies for Amputation: A Topical Review. Pain Med. 2017 Mar 1;18(3):504-519. doi: 10.1093/pm/pnw110.

Capdevila X, Bringuier S, Borgeat A. Infectious risk of continuous peripheral nerve blocks. Anesthesiology. 2009 Jan;110(1):182-8. doi: 10.1097/ALN.0b013e318190bd5b. No abstract available.

Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003 Aug;97(2):534-540. doi: 10.1213/01.ANE.0000068822.10113.9E.

Ilfeld BM, Duke KB, Donohue MC. The association between lower extremity continuous peripheral nerve blocks and patient falls after knee and hip arthroplasty. Anesth Analg. 2010 Dec;111(6):1552-4. doi: 10.1213/ANE.0b013e3181fb9507. Epub 2010 Oct 1.

Ilfeld BM, Grant SA. Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation for Postoperative Analgesia: Could Neurostimulation Replace Continuous Peripheral Nerve Blocks? Reg Anesth Pain Med. 2016 Nov/Dec;41(6):720-722. doi: 10.1097/AAP.0000000000000481. No abstract available.

Ilfeld BM, Gabriel RA, Saulino MF, Chae J, Peckham PH, Grant SA, Gilmore CA, Donohue MC, deBock MG, Wongsarnpigoon A, Boggs JW. Infection Rates of Electrical Leads Used for Percutaneous Neurostimulation of the Peripheral Nervous System. Pain Pract. 2017 Jul;17(6):753-762. doi: 10.1111/papr.12523. Epub 2016 Nov 11.

Ilfeld BM, Ball ST, Gabriel RA, Sztain JF, Monahan AM, Abramson WB, Khatibi B, Said ET, Parekh J, Grant SA, Wongsarnpigoon A, Boggs JW. A Feasibility Study of Percutaneous Peripheral Nerve Stimulation for the Treatment of Postoperative Pain Following Total Knee Arthroplasty. Neuromodulation. 2019 Jul;22(5):653-660. doi: 10.1111/ner.12790. Epub 2018 Jul 19.

Ilfeld BM, Gabriel RA, Said ET, Monahan AM, Sztain JF, Abramson WB, Khatibi B, Finneran JJ 4th, Jaeger PT, Schwartz AK, Ahmed SS. Ultrasound-Guided Percutaneous Peripheral Nerve Stimulation: Neuromodulation of the Sciatic Nerve for Postoperative Analgesia Following Ambulatory Foot Surgery, a Proof-of-Concept Study. Reg Anesth Pain Med. 2018 Aug;43(6):580-589. doi: 10.1097/AAP.0000000000000819.

Ilfeld BM, Finneran JJ 4th, Gabriel RA, Said ET, Nguyen PL, Abramson WB, Khatibi B, Sztain JF, Swisher MW, Jaeger P, Covey DC, Meunier MJ, Hentzen ER, Robertson CM. Ultrasound-guided percutaneous peripheral nerve stimulation: neuromodulation of the suprascapular nerve and brachial plexus for postoperative analgesia following ambulatory rotator cuff repair. A proof-of-concept study. Reg Anesth Pain Med. 2019 Mar;44(3):310-318. doi: 10.1136/rapm-2018-100121. Epub 2019 Feb 15.

Gilmore C, Ilfeld B, Rosenow J, Li S, Desai M, Hunter C, Rauck R, Kapural L, Nader A, Mak J, Cohen S, Crosby N, Boggs J. Percutaneous peripheral nerve stimulation for the treatment of chronic neuropathic postamputation pain: a multicenter, randomized, placebo-controlled trial. Reg Anesth Pain Med. 2019 Jun;44(6):637-645. doi: 10.1136/rapm-2018-100109. Epub 2019 Apr 5.

Gilmore CA, Ilfeld BM, Rosenow JM, Li S, Desai MJ, Hunter CW, Rauck RL, Nader A, Mak J, Cohen SP, Crosby ND, Boggs JW. Percutaneous 60-day peripheral nerve stimulation implant provides sustained relief of chronic pain following amputation: 12-month follow-up of a randomized, double-blind, placebo-controlled trial. Reg Anesth Pain Med. 2019 Nov 17:rapm-2019-100937. doi: 10.1136/rapm-2019-100937. Online ahead of print.

Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38.

Dworkin RH, Turk DC, Wyrwich KW, Beaton D, Cleeland CS, Farrar JT, Haythornthwaite JA, Jensen MP, Kerns RD, Ader DN, Brandenburg N, Burke LB, Cella D, Chandler J, Cowan P, Dimitrova R, Dionne R, Hertz S, Jadad AR, Katz NP, Kehlet H, Kramer LD, Manning DC, McCormick C, McDermott MP, McQuay HJ, Patel S, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Revicki DA, Rothman M, Schmader KE, Stacey BR, Stauffer JW, von Stein T, White RE, Witter J, Zavisic S. Interpreting the clinical importance of treatment outcomes in chronic pain clinical trials: IMMPACT recommendations. J Pain. 2008 Feb;9(2):105-21. doi: 10.1016/j.jpain.2007.09.005. Epub 2007 Dec 11.

Linacre JM, Heinemann AW, Wright BD, Granger CV, Hamilton BB. The structure and stability of the Functional Independence Measure. Arch Phys Med Rehabil. 1994 Feb;75(2):127-32.

Anagnostis C, Gatchel RJ, Mayer TG. The pain disability questionnaire: a new psychometrically sound measure for chronic musculoskeletal disorders. Spine (Phila Pa 1976). 2004 Oct 15;29(20):2290-302; discussion 2303. doi: 10.1097/01.brs.0000142221.88111.0f.

Massarweh NN, Kaji AH, Itani KMF. Practical Guide to Surgical Data Sets: Veterans Affairs Surgical Quality Improvement Program (VASQIP). JAMA Surg. 2018 Aug 1;153(8):768-769. doi: 10.1001/jamasurg.2018.0504. No abstract available.

Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Leong M, Levy RM, Abejon D, Buchser E, Burton A, Buvanendran A, Candido K, Caraway D, Cousins M, DeJongste M, Diwan S, Eldabe S, Gatzinsky K, Foreman RD, Hayek S, Kim P, Kinfe T, Kloth D, Kumar K, Rizvi S, Lad SP, Liem L, Linderoth B, Mackey S, McDowell G, McRoberts P, Poree L, Prager J, Raso L, Rauck R, Russo M, Simpson B, Slavin K, Staats P, Stanton-Hicks M, Verrills P, Wellington J, Williams K, North R; Neuromodulation Appropriateness Consensus Committee. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. Neuromodulation. 2014 Aug;17(6):515-50; discussion 550. doi: 10.1111/ner.12208.

Deer TR, Naidu R, Strand N, Sparks D, Abd-Elsayed A, Kalia H, Hah JM, Mehta P, Sayed D, Gulati A. A review of the bioelectronic implications of stimulation of the peripheral nervous system for chronic pain conditions. Bioelectron Med. 2020 Apr 24;6:9. doi: 10.1186/s42234-020-00045-5. eCollection 2020.

Rauck RL, Cohen SP, Gilmore CA, North JM, Kapural L, Zang RH, Grill JH, Boggs JW. Treatment of post-amputation pain with peripheral nerve stimulation. Neuromodulation. 2014 Feb;17(2):188-97. doi: 10.1111/ner.12102. Epub 2013 Aug 15.

Bruce J, Quinlan J. Chronic Post Surgical Pain. Rev Pain. 2011 Sep;5(3):23-9. doi: 10.1177/204946371100500306.

Imani F. Postoperative pain management. Anesth Pain Med. 2011 Jul;1(1):6-7. doi: 10.5812/kowsar.22287523.1810. Epub 2011 Jul 1. No abstract available.

Borghi B, D'Addabbo M, White PF, Gallerani P, Toccaceli L, Raffaeli W, Tognu A, Fabbri N, Mercuri M. The use of prolonged peripheral neural blockade after lower extremity amputation: the effect on symptoms associated with phantom limb syndrome. Anesth Analg. 2010 Nov;111(5):1308-15. doi: 10.1213/ANE.0b013e3181f4e848. Epub 2010 Sep 29.

Columbo JA, Davies L, Kang R, Barnes JA, Leinweber KA, Suckow BD, Goodney PP, Stone DH. Patient Experience of Recovery After Major Leg Amputation for Arterial Disease. Vasc Endovascular Surg. 2018 May;52(4):262-268. doi: 10.1177/1538574418761984. Epub 2018 Mar 1.

Houghton AD, Nicholls G, Houghton AL, Saadah E, McColl L. Phantom pain: natural history and association with rehabilitation. Ann R Coll Surg Engl. 1994 Jan;76(1):22-5.

Gallagher P, Allen D, Maclachlan M. Phantom limb pain and residual limb pain following lower limb amputation: a descriptive analysis. Disabil Rehabil. 2001 Aug 15;23(12):522-30. doi: 10.1080/09638280010029859.

Raichle KA, Hanley MA, Molton I, Kadel NJ, Campbell K, Phelps E, Ehde D, Smith DG. Prosthesis use in persons with lower- and upper-limb amputation. J Rehabil Res Dev. 2008;45(7):961-72. doi: 10.1682/jrrd.2007.09.0151.

Armaghani SJ, Lee DS, Bible JE, Archer KR, Shau DN, Kay H, Zhang C, McGirt MJ, Devin CJ. Preoperative opioid use and its association with perioperative opioid demand and postoperative opioid independence in patients undergoing spine surgery. Spine (Phila Pa 1976). 2014 Dec 1;39(25):E1524-30. doi: 10.1097/BRS.0000000000000622.

Smith SR, Bido J, Collins JE, Yang H, Katz JN, Losina E. Impact of Preoperative Opioid Use on Total Knee Arthroplasty Outcomes. J Bone Joint Surg Am. 2017 May 17;99(10):803-808. doi: 10.2106/JBJS.16.01200.

Albright-Trainer B, Phan T, Trainer RJ, Crosby ND, Murphy DP, Disalvo P, Amendola M, Lester DD. Peripheral nerve stimulation for the management of acute and subacute post-amputation pain: a randomized, controlled feasibility trial. Pain Manag. 2022 Apr;12(3):357-369. doi: 10.2217/pmt-2021-0087. Epub 2021 Nov 11.