Low Back Pain Medical Monotherapies

This article is still missing information.

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.

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 12/100, 3/100, and 7/100. 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 relaxants nor benzodiazepines have evidence to support their use in chronic low back pain. The longest follow was 30 days for Tinzanidine vs Epirisone. 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 pain, and clear evidence that pregabalin doesn't work for radicular pain. 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. 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. For people already on opioids there is no worsening of pain with ceasing their use. (See Opioid Deprescribing). Furthermore, there is no benefit compared to NSAIDs or antidepressants. Aberrant drug taking behaviours occur in up to 24% of patients with chronic low back pain. 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 trials

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.

Injection Therapies

Epidural Steroid Injections

• Probably slightly reduce leg pain and disability in the short term, 25 trials, evidence quality moderate.
• MD may not be clinically significant at less than 10%
• Leg pain: MD -4.93 (0 to 100 scale) at 2 weeks to 3 months
• Disability: MD -4.18 (0 to 100 scale) at 2 weeks to 3 months
• Apparently some controversy as to trial selection in the Cochrane metaanalysis.
• For back pain, probably no effect
• Bogduk in 2002 said there were issues at the time of trials mixing up radicular pain and back pain but they seem to be well separated in the Cochrane 2020 meta-analysis.

Tender Point Injections

Malanga and Wolff in 2008 describe the technique as follows: " It described 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 TrP 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. They noted that the best responses to injection were found when the ‘‘local twitch response’’ was provoked by impaling the active point "

• Possibly effective in the short term.
  • Kocak 2018: TPI superior to i.v. NSAID at 60 mins for acute back pain
  • Garvey 1989: TPI at least as effective as cold spray + acupressure
  • Malanga 2008: Narrative review, limited evidence beyond the short term.
  • 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
  • Miyakoshi 2007: bilateral L4/5 total dorsal rami block (5mL each side mepivacaine) by CT better than TPI at 7 days for CLBP in elderly.
  • They note "The facet joints, back muscles, fascia, ligaments, and skin of the low back region are all innervated by the medial, intermediate, and/or lateral branches of the lumbar dorsal rami. Each dorsal ramus of the lumbar spinal nerve divides into three branches: medial, intermediate, and lateral branches [10,11] (Fig. 1). These three branches principally innervate three major longitudinal back muscles: multifidus, longissimus, and iliocostalis, respectively [10,11]. Furthermore, deep to multifidus, articular branches from the medial branch innervate the facet joints above and below theoretically, all the low back pains originating from myofascial structures [1], facet joint [9,12,13], or both should be alleviated by blocking all three branches of the lumbar dorsal ramus. They confirmed spread over both adjacent branches using contrast of medial branches plus intermediate and lateral branches"

Prolotherapy

• Nonspecific low back pain – probably not effective
  • Cochrane 2007 (5 studies) 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
  • Best study Yelland 2004: n=110 CLBP, 20% dextrose/lignocaine repeated over 6 months, 2 year follow up, significant improvements in pain and disability but no different to saline Cochrane 2007, Yelland 2004. At 12 months, the proportions achieving more than 50% reduction in pain from baseline by injection group were glucose-lignocaine: 0.46 versus saline: 0.36 they also randomised to do flexion/extension exercises and there was no benefit.
• Sacroiliac Joint Pain
  • 1 x positive study. prolotherapy vs steroid (intraarticular), n = 48
  • Inclusion: sacroiliac joint pain >3 months, confirmed by fluoroscopic block (pain decrease of 50%). Pain just below PSIS and positive Patrick or Gaenslens test and pain reduction >50% with bupivacaine injection fluoroscopic
  • Exposure: 2.5mL of 25% dextrose with bupivacaine into SI joint (fluoroscopically) every two weeks up to three times until pain relief at least 90%.
  • Control: same but with triamcinolone 40mg
  • Results: Significant sustained improvements for prolotherapy
• Botox
  • May provide partial relief of pain, with no data beyond 2 months
  • Three studies, with Foster et al being the best one. The other two have significant problems.
  • Cost is $1100 for 2 vials (200 units) for the dose used in Foster et al study. Not covered by ACC or Southern Cross for this indication.

Injection Therapies Bottom Line

• Epidural Steroid Injections
  • Low to moderate quality evidence that probably works for radicular leg pain but effect size may not be clinically significant.
  • They generally don’t have a role for back pain.
• Tender Point Injections
  • low quality evidence that effective in the short term for acute pain.
  • Interesting concept of total dorsal rami blocks.
• Prolotherapy
  • 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
  • low quality evidence that effective in the short term

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

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