Low Back Pain Medical Monotherapies

==Drug Therapies==
Paracetamol: For acute low back pain it is not more effective than placebo. There is no published evidence for chronic low back pain.Saragiotto BT, Machado GC, Ferreira ML, Pinheiro MB, Abdel Shaheed C, Maher CG. Paracetamol for low back pain. Cochrane Database Syst Rev. 2016 Jun 7;2016(6):CD012230. doi: 10.1002/14651858.CD012230. PMID: 27271789; PMCID: PMC6353046.
NSAIDs: these agents appear to have an effect superior to placebo, but the effect is modest. The mean reductions have been reported by various reviews as 12/100Chou R, Deyo R, Friedly J, Skelly A, Weimer M, Fu R, Dana T, Kraegel P, Griffin J, Grusing S. Systemic Pharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2017 Apr 4;166(7):480-492. doi: 10.7326/M16-2458. Epub 2017 Feb 14. PMID: 28192790., 3/100,Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians, Denberg TD, Barry MJ, Boyd C, Chow RD, Fitterman N, Harris RP, Humphrey LL, Vijan S. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Apr 4;166(7):514-530. doi: 10.7326/M16-2367. Epub 2017 Feb 14. PMID: 28192789. and 7/100.Enthoven WT, Roelofs PD, Deyo RA, van Tulder MW, Koes BW. Non-steroidal anti-inflammatory drugs for chronic low back pain. Cochrane Database Syst Rev. 2016 Feb 10;2(2):CD012087. doi: 10.1002/14651858.CD012087. PMID: 26863524; PMCID: PMC7104791. From a categorical outcome viewpoint, NSAIDs increase the chances of obtaining 30% relief of pain from 30% to 50%. There is also limited benefit in function, for example one report of 0.85 on a 0 to 24 scale. Side effects limit their use. There are no NSAIDs that appears to be more effective than others.
Muscle relaxants: Neither non-benzodiazepine muscle relaxantsvan Tulder MW, Touray T, Furlan AD, Solway S, Bouter LM. Muscle relaxants for non-specific low back pain. Cochrane Database Syst Rev. 2003;2003(2):CD004252. doi: 10.1002/14651858.CD004252. PMID: 12804507; PMCID: PMC6464310.Abdel Shaheed C, Maher CG, Williams KA, McLachlan AJ. Efficacy and tolerability of muscle relaxants for low back pain: Systematic review and meta-analysis. Eur J Pain. 2017 Feb;21(2):228-237. doi: 10.1002/ejp.907. Epub 2016 Jun 22. PMID: 27329976. nor benzodiazepines have evidence to support their use in chronic low back pain. The longest follow was 30 days for Tinzanidine vs Epirisone.Rossi M, Ianigro G, Liberatoscioli G, Di Castelnuovo A, Grimani V, Garofano A, Camposarcone N, Nardi LF. Eperisone versus tizanidine for treatment of chronic low back pain. Minerva Med. 2012 Jun;103(3):143-9. PMID: 22653094. There is only some data to support the use of non-benzodiazepine muscle relaxants in acute low back pain, but not benzodiazepines, and none of the muscle relaxants that are available in New Zealand. Orphenadrine didn't meet inclusion criteria. Side effects also limit their use.
Neuromodulatory Agents: TCAs and SSRIs are no more effective than placebo on a variety of outcome measures. Likewise there is a lack of evidence for gabapentinoids for chronic low back painShanthanna H, Gilron I, Rajarathinam M, AlAmri R, Kamath S, Thabane L, Devereaux PJ, Bhandari M. Benefits and safety of gabapentinoids in chronic low back pain: A systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2017 Aug 15;14(8):e1002369. doi: 10.1371/journal.pmed.1002369. PMID: 28809936; PMCID: PMC5557428., and clear evidence that pregabalin doesn't work for radicular pain.Maher CG, Lin CWC, Mathieson S. Trial of Pregabalin for Acute and Chronic Sciatica. N Engl J Med. 2017 Jun 15;376(24):2396-7. doi: 10.1056/NEJMc1705241. PMID: 28614682. There are some reports of abuse of gabapentinoids.
Duloxetine, an SNRI, has a modest effect on pain and function, but is not available in New Zealand. However the average pain reduction was <1, and only 11.9% had >30% pain reduction. Responders tended to have early pain reduction at 2 weeks (≥15%), ≥ 2 pain sites, and be female.
Venlafaxine is available in New Zealand but has no RCT data. There is only one positive non controlled trial for both depression and CLBP.Rej S, Dew MA, Karp JF. Treating concurrent chronic low back pain and depression with low-dose venlafaxine: an initial identification of "easy-to-use" clinical predictors of early response. Pain Med. 2014 Jul;15(7):1154-62. doi: 10.1111/pme.12456. Epub 2014 Jul 4. PMID: 25040462; PMCID: PMC4111978. Although both are SNRIs, the two agents have some key pharmacological differences and so it shouldn't be assumed that venlafaxine would work, too.
Opioids: There is no role for the use of strong opioids in chronic low back pain, and many include weak opioids in this statement too.
In a mixed pain study that included patients with chronic low back pain, strong opioids are ineffective and there is even a trend for worse pain.Krebs EE, Gravely A, Nugent S, Jensen AC, DeRonne B, Goldsmith ES, Kroenke K, Bair MJ, Noorbaloochi S. Effect of Opioid vs Nonopioid Medications on Pain-Related Function in Patients With Chronic Back Pain or Hip or Knee Osteoarthritis Pain: The SPACE Randomized Clinical Trial. JAMA. 2018 Mar 6;319(9):872-882. doi: 10.1001/jama.2018.0899. PMID: 29509867; PMCID: PMC5885909. For people already on opioids there is no worsening of pain with ceasing their use.McPherson S, Lederhos Smith C, Dobscha SK, Morasco BJ, Demidenko MI, Meath THA, Lovejoy TI. Changes in pain intensity after discontinuation of long-term opioid therapy for chronic noncancer pain. Pain. 2018 Oct;159(10):2097-2104. doi: 10.1097/j.pain.0000000000001315. PMID: 29905648; PMCID: PMC6993952. (See Opioid Deprescribing). Furthermore, there is no benefit compared to NSAIDs or antidepressants.Chaparro LE, Furlan AD, Deshpande A, Mailis-Gagnon A, Atlas S, Turk DC. Opioids compared to placebo or other treatments for chronic low-back pain. Cochrane Database Syst Rev. 2013 Aug 27;(8):CD004959. doi: 10.1002/14651858.CD004959.pub4. PMID: 23983011. Aberrant drug taking behaviours occur in up to 24% of patients with chronic low back pain.Martell BA, O'Connor PG, Kerns RD, Becker WC, Morales KH, Kosten TR, Fiellin DA. Systematic review: opioid treatment for chronic back pain: prevalence, efficacy, and association with addiction. Ann Intern Med. 2007 Jan 16;146(2):116-27. doi: 10.7326/0003-4819-146-2-200701160-00006. PMID: 17227935. The idea of "pseudo-addiction" has no support base in evidence and is an obsolete term. Tramadol has a small effect but a lack of long term data, and no effect when only including registered and pre-registered trialsBack pain (chronic) treatment with tramadol. A living systematic review
Other: Agents like low-dose naltrexone and antihistamines have no high quality data to make a statement either way on their effectiveness.
===Drug Therapies Bottom Line===
* Low to moderate quality evidence that NSAIDs may have a small benefit for acute and chronic pain and function, and early response is predictive of later response
* Low quality evidence that a couple of non-benzodiazepine muscle relaxants may be effective for ALBP but aren’t available in NZ
* Low quality evidence that strong opioids have a small benefit for pain and function in the short term, but cause increased pain and addiction in the longer term.
* Moderate quality evidence that the antidepressant Duloxetine may be effective for CLBP
* Unclear role of TCAs
* Moderate quality evidence that gabapentinoids are likely not effective for CLBP or radicular pain, either in isolation or as an adjunct.
* Editorial in 2013 BMJ – No single drug will treat more than a minority of patients, but failure with one drug does not mean to expect failure with others, even within a class. Success or failure can be determined within 2-4 weeks. However evidence is still limited.
==Simple Needle Treatments==
=== Acupuncture ===
Low-quality evidence of better immediate (0-7 days) and short-term (1wk - 3mths) pain relief and functional improvement than sham or no treatment, or oral analgesics: 7- to 24-point immediate improvement in pain on 0- to 100-point scale. Moderate-quality evidence of no long-term benefit.FurlanAD, van TulderMW, CherkinD, TsukayamaH, LaoL, KoesBW, BermanBM. Acupuncture and dry-needling for low back pain. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD001351. DOI: 10.1002/14651858.CD001351.pub2.Xiang Y, He JY, Tian HH, Cao BY, Li R. Evidence of efficacy of acupuncture in the management of low back pain: a systematic review and meta-analysis of randomised placebo- or sham-controlled trials. Acupunct Med. 2020;38(1):15-24. doi:10.1136/acupmed-2017-011445Chou R, Deyo R, Friedly J, Skelly A, Hashimoto R, Weimer M, Fu R, Dana T, Kraegel P, Griffin J, Grusing S, Brodt ED. Nonpharmacologic Therapies for Low Back Pain: A Systematic Review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2017 Apr 4;166(7):493-505. doi: 10.7326/M16-2459. Epub 2017 Feb 14. PMID: 28192793.
===Tender Point Injections===
Malanga and Wolff in 2008 describe the technique of as follows: Holding the syringe in the dominant hand while palpating the trigger with the thumb or index finger of the opposite hand. Needle insertion was into the subcutaneous tissue adjacent to the [trigger point] at a 50 to 70 angle to the skin aiming at the taut band. Multiple insertions in different directions from the subcutaneous layer were ‘‘fast in’’ and ‘‘fast out’’ to probe for latent triggers. Each thrust coincided with the injection of 0.02 to 0.05 mL of injectate to a total of 0.5 to 1 mL in each TrP. Compression of the point for 2 minutes allowed hemostasis, which was followed by stretching of the muscle. Malanga G, Wolff E. Evidence-informed management of chronic low back pain with trigger point injections. Spine J. 2008 Jan-Feb;8(1):243-52. doi: 10.1016/j.spinee.2007.10.029. PMID: 18164472.
They noted that the best responses to injection were found when the ‘‘local twitch response’’ was provoked by impaling the active point.
Trigger point injections are possibly effective in the short term. In acute low back pain they are superior to intravenous NSAIDs at 60 minutes,Kocak AO, Ahiskalioglu A, Sengun E, Gur STA, Akbas I. Comparison of intravenous NSAIDs and trigger point injection for low back pain in ED: A prospective randomized study. Am J Emerg Med. 2019 Oct;37(10):1927-1931. doi: 10.1016/j.ajem.2019.01.015. Epub 2019 Jan 15. PMID: 30660342. and are at least as effective as cold spray plus acupressure.Garvey TA, Marks MR, Wiesel SW. A prospective, randomized, double-blind evaluation of trigger-point injection therapy for low-back pain. Spine (Phila Pa 1976). 1989 Sep;14(9):962-4. doi: 10.1097/00007632-198909000-00008. PMID: 2528826. There is limited evidence beyond the short term and so they have no evidence based support for chronic low back pain. It is interesting to note that the saline often used as a control in trials may contain (unless preservative-free) 0.9% benzyl alcohol
=== Total Dorsal Rami Block ===
Total dorsal rami block refers to blocking all branches of the dorsal rami - medial, intermediate, and lateral. This would theoretically cover the three major longitudinal back muscles (multifidus for medial, longissimus for intermediate, and iliocostalis for lateral), and the facet joints (medial branches). Bilateral L4/5 total dorsal rami blocks (5mL each side mepivacaine) by CT is more effective than trigger point injections at 7 days for chronic low back pain in the elderly.Miyakoshi N, Shimada Y, Kasukawa Y, Saito H, Kodama H, Itoi E. Total dorsal ramus block for the treatment of chronic low back pain: a preliminary study. Joint Bone Spine. 2007 May;74(3):270-4. doi: 10.1016/j.jbspin.2006.07.006. Epub 2007 Mar 7. PMID: 17383923. There is no long term data.
===Prolotherapy===
For undiagnosed chronic low back pain prolotherapy is probably not effective. The latest cochrane review is now quite old but concluded that prolotherapy alone is not effective for chronic low back pain. However 4/5 studies used a mixture dextrose-glycerine-phenol and no specific diagnosis.Dagenais S, Yelland MJ, Del Mar C, Schoene ML. Prolotherapy injections for chronic low-back pain. Cochrane Database Syst Rev. 2007 Apr 18;2007(2):CD004059. doi: 10.1002/14651858.CD004059.pub3. PMID: 17443537; PMCID: PMC6986690.
The best RCT for prolotherapy on undiagnosed chronic low back pain had 110 patients and compared 20% dextrose/lidocaine repeated over 6 months, with 2 year follow up. They found significant improvements in pain and disability but there was no difference to saline. At 12 months, the proportions achieving more than 50% reduction in pain was 46% for prolotherapy and 36% for saline. They also randomised to do flexion/extension exercises or normal activity and found no difference there.Yelland MJ, Glasziou PP, Bogduk N, Schluter PJ, McKernon M. Prolotherapy injections, saline injections, and exercises for chronic low-back pain: a randomized trial. Spine (Phila Pa 1976). 2004 Jan 1;29(1):9-16; discussion 16. doi: 10.1097/01.BRS.0000105529.07222.5B. PMID: 14699269.
Intra-articular sacroiliac joint prolotherapy has also been studied as a precision treatment. For 48 patients with sacroiliac joint pain (pain below PSIS, positive Patrick or Gaenslens test, and single positive fluoroscopic block with a pain decrease of 50%), fluoroscopic injection of prolotherapy was compared to steroid. The exposure group had 2.5mL of 25% dextrose injected fluoroscopically every two weeks up to three times until relief of at least 90%. The control had the same but with triamcinolone 40mg. The outcomes were the same at 3 months, but the results of the prolotherapy group were durable up to 15 months.Kim WM, Lee HG, Jeong CW, Kim CM, Yoon MH. A randomized controlled trial of intra-articular prolotherapy versus steroid injection for sacroiliac joint pain. J Altern Complement Med. 2010;16(12):1285‐1290. doi:10.1089/acm.2010.0031
=== Botox ===
Botox may provide partial relief of pain, with no data beyond 2 months. There are three published studies, with Foster et al being the best one. The other two have significant problems.Waseem Z, Boulias C, Gordon A, Ismail F, Sheean G, Furlan AD. Botulinum toxin injections for low-back pain and sciatica. Cochrane Database Syst Rev. 2011 Jan 19;(1):CD008257. doi: 10.1002/14651858.CD008257.pub2. PMID: 21249702. The cost is $1100 for 2 vials (200 units) for the dose used in Foster et al study. It is not covered by ACC or Southern Cross for this indication
===Injection Therapies Bottom Line===
*Tender Point Injections and total dorsal rami blocks have low quality evidence that effective in the short term for acute pain. 
*Prolotherapy has low quality evidence that effective in the short and long term for sacroiliac joint pain (intraarticular injections). Unclear if it is effective for other causes of back pain.
*Botox has low quality evidence that effective in the short term
==Epidural Steroid Injections==
For radicular pain there is good evidence for efficacy (see linked article). However for back pain, epidural steroids do not appear to have an effect.Oliveira CB, Maher CG, Ferreira ML, Hancock MJ, Oliveira VC, McLachlan AJ, Koes BW, Ferreira PH, Cohen SP, Pinto RZ. Epidural corticosteroid injections for lumbosacral radicular pain. Cochrane Database Syst Rev. 2020 Apr 9;4(4):CD013577. doi: 10.1002/14651858.CD013577. PMID: 32271952; PMCID: PMC7145384.
==Spinal Cord Stimulation==
Spinal cord stimulation involves placement of electrodes in the epidural space adjacent to the spinal area presumed to be the source of pain. An electric current is then applied to achieve sympatholytic and other neuromodulatory effects. The number and type of electrode leads and parameters of electrical stimulation can vary
They may be implanted percutaneously or by laminectomy. Power is supplied by implanted battery or transcutaneously through an external radiofrequency transmitter.
Implantation is a two stage process. A trial is performed, followed by permanent implantation for successful trials. High frequency/burst stimulation associated with greater benefit than conventional SCS. The pain-suppressing effect of SCS is likely related to a combination of a spinal and supraspinal mechanism (2, 31). The spinal mechanism involves antidromic activation of ascending dorsal column fibers, but SCS might also interact via orthodromic ascending fibers with descending serotoninergic pain modulatory systems.
Kirketeig 2019: good overview of the research Kirketeig T, Schultheis C, Zuidema X, Hunter CW, Deer T. Burst Spinal Cord Stimulation: A Clinical Review. Pain Med. 2019;20(Suppl 1):S31‐S40. doi:10.1093/pm/pnz003
===Tonic Stimulation===
*North 2005: n=50, persistent pain after surgery with leg pain greater or equal to back pain. SCS superior to reoperation for achieving >50% pain relief (38% v 12%)
*Kumar 2007: n=100, persistent radicular pain following surgery for herniated disc. SCS superior to “conventional medical management” for pain (48% v 9%)
*26-32% in these RCTs experienced a complication. Electrode migration, infection, generator pocket-related complications, and lead problem.
*Only been studied in Failed Back Surgery Syndrome. Turner 2010: prospective cohort study, workers compensation, no previous surgery. outcomes at 12 and 24 months no better than pain clinic management.
*No RCTs done for primary back pain. North 2005 patients had improvement in both leg and back pain.
*No placebo controlled trials for tonic stimulation, because it is impossible, because it causes paraesthesias.
===Burst Stimulation===
*Doesn't cause paraesthesias so can perform placebo controlled tirals
*De Ridder 2013: placebo controlled RCT, n=15, intractable back and limb pain. 12/15 were failed back surgery syndrome. Burst mode effective for back/limb and reducing attention to pain, tonic mode effective only for limb pain. 4 week follow up
*Schu 2014: placebo controlled RCT, n=20, FBSS with pre-existing SCS, burst stimulation superior to tonic. 3 week follow up
*Tjepkema-Cloostermans 2016: placebo controlled RCT, n=40, FBSS with pre-existing SCSS, high/low amplitude burst stimulation superior to tonic
*Deer 2017: RCT (non-placebo controlled), n=100, FBSS plus other conditions, burst superior to tonic, but 24% preferred tonic. 1 year follow up. Designed under FDA guidance.
===Attenuation===
* RCTs longest follow up is 3 years
* Nissen 2018: prospective trial of 20 years of consecutive patients, average follow up was 6 years of 224 consecutive FBSS patients.
* 75% who received a SCS after a trial period continued to use it throughout the follow up period which was 18 years in some patients
===SCS Bottom Line===
*This is a palliative treatment (improvement in pain but generally not function)
*It should only be considered for those with
**Predominant radicular pain PLUS 
**“Failed back surgery syndrome” PLUS
**Clear anatomical source of pain PLUS
**No abnormal illness behaviour PLUS
**A positive trial period with an external device
*There is a significant complication rate
*Burst stimulation is superior to tonic stimulation for most patients
*Extremely expensive with limited availability in NZ
*The evidence may change as technology improves
==Intraspinal Opioids==
* No RCTs for any non cancer pain condition after 30 years of use. $30,000 - $40,000 USD, with refills costing $500/visit in 2014
* Turner 2007 (systematic review): 41% had urinary retention, 37% required catheterisation, nausea/vomiting 33%, pruritis 26%, catheter related complications 18%, pump malposition 17%, wound infection 12%, meningitis 3%
* Loeser 2014 (Editorial):
** Very little information on the proper selection of patients
** Most studies show that those on high-dose opioids without relief are poor candidates
** Dose escalation and side effects occur with any route of delivery
** Multidisciplinary pain management is more effective and cheaper 
** May be considered for palliative care. Smith 2002: n=202, RCT, refractory cancer pain (not only back pain). Success in 84.5% vs 70.8% for comprehensive medical management.
===Intrathecal Opioids Bottom Line===
No valid use in the realm of Musculoskeletal Medicine.
==See Also==
*Low Back Pain Nonmedical Monotherapies
*:Category:Precision Techniques
==References==
Category:Lumbar Spine
Category:Partially complete articles