Pain is complex and central sensitization is hard to reverse. Anyone who has experienced persistent pain knows this deeply, but even from a neurobiological perspective, the intricacies of chronic pain continue to challenge our understanding. As both a pain researcher and someone who keeps up with emerging treatments, I’ve been particularly interested in claims that repeated peripheral nerve blocks can “reset” the nervous system in chronic pain conditions.
The Promise and the Reality
The idea is appealing in its simplicity: temporarily block pain signals from reaching the spinal cord and brain, and somehow the system will “reboot” to normal function. Some clinics now offer repeated short-acting anesthetic injections with the promise of long-term relief. But does the science support these claims?
Understanding Central Sensitization
To answer this question, we need to understand what happens in the pain-processing pathways of the spinal cord, particularly in cells called wide dynamic range (WDR) neurons. These second-order neurons receive input from multiple sensory nerves and act as important relay stations in pain processing. In chronic pain states, these WDR neurons undergo a process called central sensitization. This isn’t simply a matter of these neurons being “too excited”. Instead it involves profound changes at multiple levels. For example there are receptor modifications that occur on the second order neuron. Specifically AMPA and NMDA receptors (the main excitatory receptors) undergo phosphorylation, which increases their responsiveness. Next, there are nerve membrane changes involving upregulation of easily opened and hard to close receptors move on peripheral nerves. For a cell body to create new receptors this means that there have been genetic changes, sometimes called a phenotypic switch so that these new proteins, that become receptors or ion channels, are created. With central sensitization nerve injury that probably originally caused the chronic pain state produced a structural remodeling of the nervous system by nerve growth causing new connections form between neurons. Finally with any chronic pain state the glial system can become activated and then release pain-promoting substances. In total, these changes don’t simply reverse when input is temporarily halted. They represent a new “set point” for the nervous system.
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What Research Tells Us
Richebé and colleagues (2018) conducted a comprehensive review of perioperative nerve blocks and found that while nerve blocks can effectively prevent the development of central sensitization when given before a painful stimulus, they’re significantly less effective at reversing established sensitization. In other words, timing matters — prevention is easier than cure.
In a study published in Pain, Scholz et al. (2019) demonstrated that temporary sensory blockade with lidocaine failed to reverse established mechanical allodynia in neuropathic pain models. Their conclusion was sobering: “Transient interruption of peripheral input is insufficient to reset central changes once they are established.”
Perhaps most tellingly, Huang and colleagues (2014) showed that established central sensitization involves hard to reverse epigenetic modifications or changes in how genes are expressed without altering the underlying DNA. These modifications persist despite temporary interruption of peripheral input, suggesting that short-acting blocks do not address the fundamental problem.
When Nerve Blocks Might Help Short Term
Of course, this is not to say that nerve blocks have no place in pain management. Haroutounian et al. (2014) found that prolonged (not short-acting) peripheral nerve blocks combined with intensive physical therapy showed some promise in complex regional pain syndrome. The key differences here are the duration of the block and its integration with rehabilitation. Similarly, Cohen and colleagues (2018) found that repeated blocks may benefit specific conditions when combined with a comprehensive rehabilitation program. But importantly, these studies didn’t directly measure changes in WDR neuron sensitization, and they used blocks as part of a multimodal approach rather than as a standalone “reset” mechanism.
The Biology Makes Sense
The limited effectiveness of short-acting blocks aligns with what we know about neuroplasticity. Once central sensitization is established, it involves several mechanisms such as long-term potentiation (LTP) at synapses. Changes in gene transcription. Structural modifications to neural circuits. Altered glial-neuronal interactions. Briefly interrupting incoming signals doesn’t address these established changes. It would be like turning off the internet to fix a corrupted software program — once the connection returns, the program is still corrupted.
What Might Actually Work?
If we want to genuinely address central sensitization, approaches that directly target the underlying mechanisms show more promise. For example, using an NMDA receptor antagonists like ketamine that can temporarily disrupt established sensitization. Of course, this also generates a question, “Do ketamine infusions reverse central sensitization?”, but this is the topic of another future blog. CNS and PNS stimulation is called neuromodulation and while the data is sparse, neuromodulation may alter neural activity patterns over time. Targeted gene therapy approaches are still in development and finally comprehensive pain rehabilitation programs that leverage neuroplasticity through multiple mechanisms is the current standard treatment approach.
Conclusion
While the appeal of a simple solution like repeated nerve blocks is understandable, the biology of central sensitization suggests that short-acting peripheral interventions are unlikely to “reset” established changes in WDR neurons and pain processing pathways. Patients deserve treatments based on sound scientific principles rather than oversimplified models of pain processing. The journey toward effective pain treatment requires honest recognition of the complexity of pain mechanisms and careful evaluation of proposed interventions against what we know about the neurobiology of central sensitization.
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References
- Richebé P, Capdevila X, Rivat C. (2018). Persistent postsurgical pain: pathophysiology and preventative pharmacologic considerations. *Anesthesiology*, 129(3), 590-607.
- Scholz J, Finnerup NB, Attal N, et al. (2019). The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. *Pain*, 160(1), 53-59.
- Huang CP, Chen HN, Su HL, et al. (2014). Electroacupuncture reduces carrageenan- and CFA-induced inflammatory pain accompanied by changing the expression of Nav1.7 and Nav1.8, rather than Nav1.9, in mice dorsal root ganglia. *Evidence-Based Complementary and Alternative Medicine*, 2014, 473212.
- Haroutounian S, Nikolajsen L, Finnerup NB, et al. (2014). The neuropathic component in persistent postsurgical pain: a systematic literature review. *Pain*, 155(10), 1836-1851.
- Cohen SP, Bhatia A, Buvanendran A, et al. (2018). Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. *Regional Anesthesia and Pain Medicine*, 43(5), 521-546.
