Welcome to the eighth edition of my sciatica newsletter! This week’s podcast In this week’s podcast, I talk to Michelle Angus. Michelle is a consultant physiotherapist working for the Complex Spinal Team in the Emergency Village of a tertiary spinal referral centre at Salford Royal NHS Foundation Trust. In this podcast, she tells me about: Managing radicular pain in the ED Spinal injections Spinal surgery Medications for radicular pain And much more! So long, gabapentinoids? In the podcast, Michelle shares her clinical experience with prescribing gabapentinoids to people with acute radicular pain. Her impression is that while they do not work for everybody, some of her patients get meaningful relief. In last week's podcast, Kate told me that gabapentin helped her own radicular pain. When I asked on twitter, I heard (mostly) similar stories: "gabapentinoids are sometimes the only thing that allows my patients/allowed me to get any relief". At the time of writing, NICE guidelines for sciatica don’t make a specific recommendation on gabapentinoids; instead, they direct the reader to the general guidelines for prescribing for neuropathic pain, which approve them.  But, the draft version of the updated NICE guidelines for low back pain and sciatica (released some weeks after my conversation with Michelle) recommends against them. According to the draft update, there is no evidence to support their use for people with sciatica. Where do we go from here? Gabapentin was developed in the early 1970s. It was approved in 1993 for seizures and marketed for pain soon after. Pregabalin arrived on the scene about ten years later. In the last two decades, their use has increased dramatically. Much of this has been “off label”, and the drugs have nontrivial side effects, so this increase is a cause for concern. (Graph taken from Montastruc et al.) Together we can call gabapentin and pregabalin gabapentinoids or anti-epileptics. Sometimes the term "anti-neuropathics" is used to bundle the gabapentinoids with tricyclic antidepressants like amitriptyline.  The gabapentinoids were designed to work on GABA, an inhibitory neurotransmitter, which is where they get their name. It turns out they don't do this. Instead, it seems they primarily work on voltage gated calcium channels.  You will remember that when an action potential arrives at the axon terminal, voltage gated calcium channels open to let calcium into the neuron. The calcium causes this first neuron to release neurotransmitters into the synapse, which trigger another action potential in the second neuron. After a nerve injury, more voltage gated calcium channels are expressed on the end of the injured first neuron, so more neurotransmitter is released, so the second neuron becomes more excitable, which can increase pain.  These voltage gated calcium channels are made up of smaller sub-structures, one of which is the α2δ subunit. It's this subunit that the gabapentinoids act on. As far as I can tell, we don't know exactly how. One theory is that gabapentinoids stop the subunits from being transported to the axon terminal in the first place. With fewer α2δ subunits, one link is weakened in the chain of synaptic transmission. And so that second neuron is less excitable.  There is a good deal of evidence that gabapentinoids work fairly well for neuropathic pain. The problem is, we can’t say the same for sciatica. The draft update to the NICE guidelines refers to only three studies. One is small, lower quality and found gabapentinoids worked quite well. The other two are large, high-quality trials, and say gabapentinoids are no better than placebo.  On reading that these large, high quality studies found no benefit, my first question was: Did they select patients with *neuropathic* radicular pain? After all, r