I have looked at recent papers that focus on neuropathic pain, one of the common pain types seen in CRPS. I’m afraid that some of the research is ‘sciency’ but of course it has to be, so do not worry of you don’t fully understand the methods or the physiology. At the end of the more complex abstracts I have put a summary.
HCN2 ion channels play a central role in inflammatory and neuropathic pain.
Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, UK.
The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators of action potential firing include the HCN ion channels, which generate an inward current, I(h), after hyperpolarization of the membrane. We found that genetic deletion of HCN2 removed the cyclic adenosine monophosphate (cAMP)-sensitive component of I(h) and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specifically deleted in nociceptors expressing Na(V)1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these mice showed no neuropathic pain in response to thermal or mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-driven action potential firing in Na(V)1.8-expressing nociceptors.
The excitability of a nerve is determined by the activity of receptors that allow ions to flow in and out. The flow of ions alters the threshold of excitability meaning that it is much easier for the nerve to be stimulated and fire a signal. It is the firing of danger signals to the brain via the spinal cord that can lead to pain. When I say that it ‘can’ lead to pain, this is because sometimes the brain receives these danger signals but does not respond by producing pain. The brain must judge the signals to be a sign of danger for pain to be experienced. Neuropathic pain often includes spontaneous pain that is caused by ectopic firing of signals.
The Influence of Chinook Winds and Other Weather Patterns upon Neuropathic Pain.
Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada.
Objective. Although Chinook winds are often viewed positively during a cold prairie winter, patients suffering with neuropathic pain (NeP) anecdotally report exacerbations of NeP during Chinooks and during other weather changes. Our objective was to identify if Chinook winds lead to acute exacerbations in pain severity in a NeP patient population. Design. Prospective diary-based assessments of patients with at least moderate NeP over 6-month periods during different seasons of the year were performed. Concurrent weather conditions were tracked hourly, with Chinook winds defined using accepted meteorological definition. We also examined other aspects of weather including precipitation, temperature, and humidity. Days with acute exacerbations were defined when a daily visual analog score pain score was ≥2 points above their average NeP score over the entire 6-month period. Results. Chinooks were not associated with individual acute exacerbations in NeP. Instead, Chinook days were found to be protective against acute exacerbations in NeP (odds ratio 0.52 [0.33-0.71]). Post hoc study associated Chinooks with NeP relief (odds ratio 1.83 [1.17-2.49]). We could not identify relationship between precipitation or humidity with acute NeP exacerbation. However, days with cold temperature ≤ -14°C were associated with greater risk of NeP exacerbation. Conclusion. Weather-mediated changes occur for patients with NeP, manifesting as relief from Chinook winds while cold temperature conditions can provoke exacerbations in NeP.
Cold commonly affects neuropathic pain–worsening the symptoms–including ambient temperature or a cold stimulus applied (e.g. alcohol wipe, cold draft, ice)
Pregabalin for acute and chronic pain in adults.
Pain Research and Nuffield Department of Anaesthetics, University of Oxford, West Wing (Level 6), John Radcliffe Hospital, Oxford, Oxfordshire, UK, OX3 9DU.
Antiepileptic drugs have been used in pain management since the 1960s. Pregabalin is a recently developed antiepileptic drug also used in management of chronic neuropathic pain conditions.
To assess analgesic efficacy and associated adverse events of pregabalin in acute and chronic pain.
We searched MEDLINE, EMBASE, and CENTRAL to May 2009 for randomised controlled trials (RCTs). Additional studies were identified from the reference lists of retrieved papers and on-line clinical trial databases.
Randomised, double blind trials reporting on the analgesic effect of pregabalin, with subjective pain assessment by the patient as either the primary or a secondary outcome.
DATA COLLECTION AND ANALYSIS:
Two independent review authors extracted data and assessed trial quality. Numbers-needed-to-treat-to-benefit (NNTs) were calculated, where possible, from dichotomous data for effectiveness, adverse events and study withdrawals.
There was no clear evidence of beneficial effects of pregabalin in established acute postoperative pain. No studies evaluated pregabalin in chronic nociceptive pain, like arthritis.Pregabalin at doses of 300 mg, 450 mg, and 600 mg daily was effective in patients with postherpetic neuralgia, painful diabetic neuropathy, central neuropathic pain, and fibromyalgia (19 studies, 7003 participants). Pregabalin at 150 mg daily was generally ineffective. Efficacy was demonstrated for dichotomous outcomes equating to moderate or substantial pain relief, alongside lower rates for lack of efficacy discontinuations with increasing dose. The best (lowest) NNT for each condition for at least 50% pain relief over baseline (substantial benefit) for 600 mg pregabalin daily compared with placebo were 3.9 (95% confidence interval 3.1 to 5.1) for postherpetic neuralgia, 5.0 (4.0 to 6.6) for painful diabetic neuropathy, 5.6 (3.5 to 14) for central neuropathic pain, and 11 (7.1 to 21) for fibromyalgia.With 600 mg pregabalin daily somnolence typically occurred in 15% to 25% and dizziness occurred in 27% to 46%. Treatment was discontinued due to adverse events in 18 to 28%. The proportion of participants reporting at least one adverse event was not affected by dose, nor was the number with a serious adverse event, which was not more than with placebo.Higher rates of substantial benefit were found in postherpetic neuralgia and painful diabetic neuropathy than in central neuropathic pain and fibromyalgia. For moderate and substantial benefit on any outcome NNTs for the former were generally six and below for 300 mg and 600 mg daily; for fibromyalgia NNTs were much higher, and generally seven and above.
Pregabalin has proven efficacy in neuropathic pain conditions and fibromyalgia. A minority of patients will have substantial benefit with pregabalin, and more will have moderate benefit. Many will have no or trivial benefit, or will discontinue because of adverse events. Individualisation of treatment is needed to maximise pain relief and minimise adverse events. There is no evidence to support the use of pregabalin in acute pain scenarios.
This is a Cochrane Review meaning that a number of research papers are analysed before concluding whether a treatment is effective or not.
Genotype-selective phenotypic switch in primary afferent neurons contributes to neuropathic pain.
Department of Medical Neurobiology, Faculties of Medicine and Dentistry, The Hebrew University of Jerusalem, Jerusalem, Israel.
Pain is normally mediated by nociceptive Aδ and C fibers, while Aβ fibers signal touch. However, after nerve injury, Aβ fibers may signal pain–this means that touch now hurts. Using a genetic model, we tested the hypothesis that phenotypic switching in neurotransmitters expressed by Aβ afferents might account for heritable differences in neuropathic pain behavior. The study examined selection-line rats in which one line, high autotomy (HA)–rats chewing themselves as a pain behaviour–, shows higher levels of spontaneous pain in the neuroma neuropathy model, and of tactile allodynia in the spinal nerve ligation (SNL) model, than the companion low autotomy (LA) line. Changes in calcitonin gene-related peptide (CGRP) and Substance P–peptides released by cells that cause excitability– expression were evaluated immunohistochemically in L4 and L5 dorsal root ganglia 7days after SNL surgery. Expression of CGRP was decreased in axotomized small- and medium-diameter neurons in both rat lines. However, in HA but not in LA rats, there was a tenfold increase in CGRP immunoreactivity (CGRP-IR) in large-diameter neurons. Corresponding changes in CGRP-IR in axon terminals in the nucleus gracilis were also seen. Finally, there were indications of enhanced CGRP neurotransmission in deep laminae of the dorsal horn. Substance P immunoreactivity was also upregulated in large-diameter neurons, but this change was similar in the 2 lines. Our findings suggest that phenotypic switching contributes to the heritable difference in pain behavior in HA vs LA rats. Specifically, we propose that in HA rats, but less so in LA rats, injured, spontaneously active Aβ afferents both directly drive CGRP-sensitive central nervous system pain-signaling neurons and also trigger and maintain central sensitization, hence generating spontaneous pain and tactile allodynia.
Spontaneous pain and pain from light touch is due to genetic changes in the nerve cells of Aß afferent (sensory) nerves.
A classic paper
Neuropathic pain: redefinition and a grading system for clinical and research purposes.
Institute of Physiology and Pathophysiology, Johannes Gutenberg University, Mainz, Germany.
Pain usually results from activation of nociceptive afferents by actually or potentially tissue-damaging stimuli. Pain may also arise by activity generated within the nervous system without adequate stimulation of its peripheral sensory endings. For this type of pain, the International Association for the Study of Pain introduced the term neuropathic pain, defined as “pain initiated or caused by a primary lesion or dysfunction in the nervous system.” While this definition has been useful in distinguishing some characteristics of neuropathic and nociceptive types of pain, it lacks defined boundaries. Since the sensitivity of the nociceptive system is modulated by its adequate activation (e.g., by central sensitization), it has been difficult to distinguish neuropathic dysfunction from physiologic neuroplasticity. We present a more precise definition developed by a group of experts from the neurologic and pain community: pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This revised definition fits into the nosology of neurologic disorders. The reference to the somatosensory system was derived from a wide range of neuropathic pain conditions ranging from painful neuropathy to central poststroke pain. Because of the lack of a specific diagnostic tool for neuropathic pain, a grading system of definite, probable, and possible neuropathic pain is proposed. The grade possible can only be regarded as a working hypothesis, which does not exclude but does not diagnose neuropathic pain. The grades probable and definite require confirmatory evidence from a neurologic examination. This grading system is proposed for clinical and research purposes.
In my view there are many cases of neuropathic pain (NP) that are not identified, mainly because the examiner is not looking for this pain type. This paper considers whether NP exists in anterior knee pain–it does in my experience. I see a large number of people with back complaints and is it not uncommon to find NP hiding in there, often obscured by a more mechanical or inflammatory pain mechanism. Using clinical tests and a measure or two, we can convert suspicion to reality and then consider how this pain type needs to be managed. There are different implications when NP is present including the prognosis. It takes longer to settle down and flare-ups are common. Flare-ups need effective management including self-care strategies to move through these difficultly times effectively. RS
Is pain in patellofemoral pain syndrome neuropathic?
Section for Physiotherapy Science, Department of Public Health and Primary Health Care, University of Bergen, Kalfarveien, Bergen, Norway. email@example.com
There is no consensus among experts regarding the etiology or management of patellofemoral pain syndrome (PFPS). Observations indicating dysfunction of the peripheral nervous system around the patellae have been reported. To what extent these sensory abnormalities cause pain has so far not been investigated. The aim of this study was to assess whether a subgroup of patients with unilateral PFPS have neuropathic pain related to the painful knee.
A total of 91 patients with unilateral PFPS, between 18 and 40 years of age, and a comparable group of 23 healthy participants aged 18 to 44 years were included. Level of knee function, pain intensity, and qualities were assessed. Somatosensory assessments were carried out by bedside neurologic tests and quantitative sensory testing, assessing thermal, tactile, and vibration thresholds.
Ample signs of sensory aberrations with considerable heterogeneity and overlap regarding the degree and type of dysfunction of the nervous system were found in the painful area of the PFPS patients. No clear subgroup of patients with neuropathic pain or clustering of features related to neuropathic pain was identified.
This study hypothesizes that the observed sensory aberrations may cause neuropathic pain in patients with PFPS. There is no validated method for subgrouping patients with possible neuropathic pain and in this study considerable heterogeneity and overlap regarding signs and symptoms of neuropathic pain made subgrouping even more difficult. A mechanism-based understanding of the pain is, however, essential for the selection of adequate treatment strategies in painful musculoskeletal disorders.