CRF vs WCRF or PRF-DRG in CLBP of FJ Origin and RFA Failure of MBDR: Central Sensitization and Aberrant Nerve Sprouting
CRF vs WCRF or PRF-DRG in CLBP of FJ Origin and RFA Failure of MBDR: Central Sensitization and Aberrant Nerve Sprouting
The investigators will select two study groups from a population of patients with severe
 chronic low back pain (CLBP) of facet joint (FJ) origin already treated with conventional
 radiofrequency ablation (CRFA) of the medial branch of the dorsal ramus (MBDR) and that
 failed to obtain a 50% pain reduction measured through the numerical rate scale (NRS) for at
 least 3 months. Severe CLBP is considered a value of at least 7 by NRS pain assessment.

 The first group will be characterized by a nociceptive/mechanic type of back pain. The second
 group of study will be characterized by a neuropathic type of back pain. This difference will
 be established by a DN4 score of at least 4 points (Doleur Neurophatique 4).

 The patients in the group with nociceptive/mechanic back pain will be randomly assigned to
 conventional radiofrequency ablation or to water cooled radiofrequency (WCRF) of the MBDR.
 The patients in the group with neuropathic back pain will be randomly assigned CRFA of MBDR
 or to pulsed radiofrequency (PRF) of the dorsal root ganglia (DRG).

 The study will be carried on for an estimated time of 3 years.

 Primary outcomes will be:

 -  at least 50% back pain reduction for at least 3 months evaluated through NRS, with a
 subcategorization of results that will consider a mean difference in effect (respect to
 the initial evaluation, with an initial NRS score of at least 7) of 1 point on NRS pain
 scale as small/modest, 2 points as moderate, more than 2 as large/substantial between
 the case/control study groups.

 -  improvement of low back pain disability: 10 points increase on the Oswestry Low Back
 Pain Disability Questionnaire (ODI) have been proposed as minimal clinically important
 differences, between 10 and 20 as moderate, more than 20 as large/substantial clinical
 improvement at month 3 and 6.

 Secondary outcome will be evaluated by the 12-item short form survey SF12, accordingly with
 the clinical pre-interventional findings, analgesic intake at month 1-3-6 (if increased,
 unchanged, decreased, in dosages or number of pain killers' assumption). Groups sizes: will
 be calculated based on the disease's incidence and the outcome targets.
The efficacy of radiofrequency to treat LBP of FJ origin decreases with time, and the
 pathophysiological mechanisms behind this failure is a matter of debate; the phenomenon of
 central sensitization and ectopic nerve regeneration could be possible explanations.

 Central sensitization represents an enhancement in the function of neurons and circuits in
 nociceptive pathways caused by increases in membrane excitability and synaptic efficacy as
 well as to reduced inhibition and is a manifestation of the remarkable plasticity of the
 somatosensory nervous system in response to activity, inflammation, and neural injury. The
 net effect of central sensitization is to recruit previously subthreshold synaptic inputs to
 nociceptive neurons, generating an increased or augmented action potential output: a state of
 facilitation, potentiation, augmentation, or amplification. Central sensitization is
 responsible for many of the temporal, spatial, and threshold changes in pain sensibility in
 acute and chronic clinical pain settings and exemplifies the fundamental contribution of the
 central nervous system to the generation of pain hypersensitivity. Because central
 sensitization results from changes in the properties of neurons in the central nervous
 system, the pain is no longer coupled, as acute nociceptive pain is, to the presence,
 intensity, or duration of noxious peripheral stimuli. Instead, central sensitization produces
 pain hypersensitivity by changing the sensory response elicited by normal inputs, including
 those that usually evoke innocuous sensations.

 In previous studies using animal models of low back pain, mechanical allodynia has been
 correlated with and is hypothesized to be due to a host of physiologic changes in the central
 nervous system. Among these nociceptive responses are neuronal plasticity, glial cell
 activation and cytokine upregulation. In addition, animal models specifically investigating
 changes in neural electrical activity following lumbar facet capsule stretching have
 demonstrated alterations in neurophysiology for applied loading. Together, these molecular
 and cellular changes contribute to central sensitization and persistent pain. Indeed, in
 clinical research, central sensitization has been hypothesized as a mechanism of chronic pain
 after whiplash injury.

 Injury to the cervical facet joint and its capsule is primarily a ligamentous injury but
 because the facet capsule is innervated there may also be neuropathic injury. In fact,
 capsule stretch in several animal models induces both transient increases in firing of
 joint-innervating afferents similar to the injury discharge that accompanies nerve injury and
 also the later development of ectopic firing and hyperexcitability in dorsal horn neurons.
 The onset of spontaneous firing likely represents a temporal threshold after which
 sensitization persists despite blockade of joint afferent activity with nerve blocks or
 neurotomy.

 Patients with chronic pain exhibit primary mechanical hyperalgesia over the back of the
 cervical spine, in a "coat hanger" distribution indicative of peripheral nociceptor
 sensitization. These patients are also hypersensitive to pressure, heat, and cold stimuli at
 sites distant from the cervical spine, including over the median, radial, and ulnar nerve
 trunks in the arm and over the tibialis anterior muscle. Together, these studies demonstrate
 that generalized and widespread secondary hypersensitivity is robust in individuals who
 sustain a whiplash-like exposure and indicative of central sensitization. Patient-reported
 sensory disturbances include spontaneous pain that is disproportionate to and/or occurs in
 the absence of any inciting event.

 There are more than two dozen reported cases of lumbar facet dislocation after rapid
 deceleration injuries (e.g., traffic accidents), most involving L5-S1. The mechanism of
 injury in these cases is purported to be a combination of hyperflexion, distraction, and
 rotation. In a posthumous study conducted in 31 lumbar spines of subjects who died of
 traumatic injuries (mostly motor vehicle accidents), Twomey et al. found occult bony
 fractures in the superior articular process or subchondral bone plate in 35% of victims, and
 z-joint capsular and/or articular cartilage damage in 77% of cases. In this study the authors
 concluded that occult bony and soft tissue injuries to the l-z joints may be a common cause
 of LBP after trauma.

 In addition to immediate neuronal responses, facet capsular loading that induces behavioural
 hypersensitivity in the rat is also associated with many sustained modifications in the
 nociceptive signalling from the primary afferents that are evident in the DRG.

 Protein expression of the nociceptive neurotransmitter, substance P, is increased in the DRG
 after painful facet joint stretch by day 7, and that change is absent in non-painful stretch.
 Capsular stretch-induced increases in DRG expression of the metabotropic glutamate receptor 5
 (mGluR5) and its second messenger, protein kinase C-epsilon (PKCε), are strain dependent and
 are not evident until 7 days after the initial injury. The late upregulation of these
 molecules suggests that they may play a role in the later nociceptive pathways involved in
 injury-induced pain. Because these neuromodulators are involved in neuroplasticity and pain,
 their delayed elevation implies that the afferents undergo persistent activation and/or
 dysfunction after painful loading has occurred. Because axonal degeneration is known to take
 7 days to develop, it may contribute to the late onset of modified nociceptive signalling.

 In addition to increases in expression of glutamate receptors, expression of glutamate
 transporters on astrocytes and neurons, which regulate the clearance of glutamate away from
 synapses, like glutamate aspartate transporter, glutamate transporter 1, and excitatory
 amino-acid carrier 1, is also altered in the spinal cord 1 week after painful facet stretch.
 While the astrocyte glutamate transporter (glutamate aspartate transporter) is upregulated 1
 week after painful injury, both glutamate transporter 1 and excitatory amino-acid carrier 1,
 which are expressed on other cells, are downregulated, pointing to the widespread and
 complicated dysregulation of glutamate in pain from facet joint injury.

 Like other chronic pain conditions, spinal astrocytes are activated for at least 14 days
 after painful facet stretch. Mechanical injury to the facet capsule also regulates the
 production of inflammatory mediators, including proinflammatory cytokines and neurotrophins,
 in the facet joint itself, as well as in the DRG. Because peripheral inflammation increases
 hyperexcitability and substance P in DRG neurons, along with pain production, recent studies
 have begun to elucidate the molecular mechanisms by which peripheral inflammation contributes
 to central sensitization in the context of facet-mediated pain. Recently, neurotrophins have
 been implicated both locally in the facet and to be more widespread in the CNS. Nerve growth
 factor (NGF) increases in the facet joint tissues as early as 1 day after a facet joint
 distraction that produces pain at that same time. Further, inhibiting NGF signalling also
 prevents the onset of pain and associated spinal neuron hyperexcitability when anti-NGF is
 given intra-articularly immediately after capsule stretch and before pain develops,
 suggesting a critical role of local NGF in initiating pain. Unlike NGF, expression of the
 neurotrophin brain-derived neurotrophic factor (BDNF) increases in both the DRG and spinal
 cord at a later time (day 7), with intrathecal administration of the BDNF-sequestering
 molecule trkB-Fc after facet injury partially reducing pain. Collectively, these NGF and BDNF
 studies not only reveal important novel pathways emerging as having critical roles in pain
 from whiplash injury, but also provide potential therapeutic targets for treating joint pain.

 Histologic studies have demonstrated that the lumbar facet joints are richly innervated with
 encapsulated (Ruffini-type endings, Pacinian corpuscles), un-encapsulated, and free nerve
 endings. The presence of low-threshold, rapidly adapting mechanosensitive neurons suggests
 that in addition to transmitting nociceptive information, the l-z facet capsule also serves a
 proprioceptive function. Besides substance P and calcitonin gene-related peptide, a
 substantial percentage of nerve endings in facet capsules have also been found containing
 neuropeptide Y, indicating the presence of sympathetic efferent fibers. Nerve fibers have
 also been found in subchondral bone and intra-articular inclusions of l-z joints, signifying
 that facet-mediated pain may originate in structures besides the joint capsule. In
 degenerative lumbar spinal disorders, inflammatory mediators such as prostaglandins and the
 inflammatory cytokines interleukin 1, interleukin 6, and tumor necrosis factor alpha have
 been found in facet joint cartilage and synovial tissue.

 Wide dynamic range neurons in the dorsal horn may be capable of modulating central
 sensitization in many chronic pain states. In their study K.P.Quinn et al. comparing painful
 to non-painful and sham C6/C7 cervical facet joint capsule stretch stimuli in a rat model
 find out that the proportion of cells in the deep laminae that responded as wide dynamic
 range neurons was increased in the painful group relative to non-painful or sham groups
 (p<0.0348).

 The significant increase in the number of wide dynamic range neurons classified in the
 painful group (69% of neurons; p>0.0348) in this study suggests that a phenotypic shift in
 the response of the neuronal population in the deep laminae of the dorsal horn may play a key
 role in modulating chronic pain after facet joint injury.

 These findings suggest that excessive facet capsule stretch, while not producing visible
 tearing, can produce functional plasticity of dorsal horn neuronal activity. The increase in
 neuronal firing across a range of stimulus magnitudes observed at day 7 post-injury that
 facet-mediated chronic pain following whiplash injury is driven, at least in part, by central
 sensitization.

 Despite the fact that most of the neurophysiological and molecular central and peripheral
 changes in the low back pain syndrome are related to rat experimental whiplash-like exposure,
 the investigators consider that the mechanisms of central sensitization related to chronic
 low back pain of FJ origin can be hypothesised to be the same.

 On the other side, the mechanism of aberrant nerve sprouting after previous RFA could explain
 the necessity to increase the size of the lesion, especially in patients that underwent to
 multiple treatment with such technique.

 Pain recurrence after denervation in medical practice, and nerve regeneration from a third
 degree nerve injury from different ablation techniques, have a common pathway. This pathway
 includes macrophage migration, Schwann cell proliferation, CAMs for preparing the basement
 membrane, NGF on the Schwann cell for axonal sprouting, and increased trophic factors.

 Injured axons regenerate at a rate of 1-2 mm/day, although the rate depends on many factors
 and can vary significantly from individual to individual. Since the length of nerve from the
 axonal lesion to the lumbar facet joint is approximately 30-40 mm, reinnervation could occur
 within 3-6 weeks. Regeneration is the primary form of nerve repair when >90% of the axons are
 injured. In partial nerve injuries when only 20%-30% of the axons are affected, collateral
 sprouting from preserved axons can contribute to reinnervation. Okuyama et al. showed that
 radiofrequency ablation in cardiac tissue results in aberrant nerve sprouting within 2 hours
 after ablation. Therefore, ablation of nerves within the back could have a high likelihood
 for a similar development, which could cause faster failure rates.

 In conclusion this study will select two groups of patients from a population with severe
 chronic low back pain (CLBP) of facet joint (FJ) origin already treated with conventional
 radiofrequency ablation (CRFA) of the medial branch of the dorsal rama (MBDR) and that failed
 to obtain at least a 50% pain reduction measured through the numerical rate scale (NRS).
 Severe CLBP is considered a patient subjective pain judgement superior to 7 by NRS
 evaluation.

 The first group will be characterized by a nociceptive/mechanic type of back pain. The second
 group of study will be characterized by a neuropathic type of back pain. This difference will
 be established by a DN4 score superior to 4 points (Doleur Neurophatique 4) and a negative
 pre-interventional eco-guided medial branch block (MBB). A negative MBB will be characterized
 by a reduction of NRS inferior to 50%.

 The aim of this study is to try to clarify if a larger lesion created by the water cooled
 radiofrequency (WCRF) in the nociceptive/mecchanic pain groups (NMPG) and the pulsed
 radiofrequency (PRF) of dorsal root ganglia (DRG) in the neuropatic pain groups (NPPG) could
 improve patients' functional status and reduce the burden of their low back pain compared to
 conventional radiofrequency (CRF) of the medial brach of the dorsal rama (MBDR).

 If the hypothesis in study are confirmed there is to be expected a statistically significant
 reduction in the NRS and an improvement in the ODI score in the DRG-PRF and WCRF groups,
 compared to the patients in the CRF groups. The aim is to allow the patients to start a
 program of rehabilitation/physiotherapy, that is by far the standard of clinical care for LBP
 syndrome.

 In this case the results could support our hypothesis in both group of investigations.

 Like already underlined in the physiopathological explanation representing the base of this
 study, increasing the area of lesion with the WCRF technique should increase the chances to
 target the arborized neural regenerate terminals to the zygapophyseal joint, leading to a
 better result and possibly longer efficacy of the procedure in the NMPG respect to the group
 treated with CRF. Today, different doctors use both techniques based on their personal
 preference and logistic possibility as there are no conclusive data about superiority; even
 the last consensus practice guidelines for lumbar facet joint pain proposed by the American
 Society of Regional Anesthesia and Pain Medicine 2020 (CPG-ASRAPM) assess that "there is
 indirect evidence, and limited direct evidence, that techniques that result in larger lesions
 (eg, larger electrodes, higher temperatures, longer heating times, proper electrode
 orientation, fluid modulation) improve outcomes" (Grade C, low level of certainty that larger
 lesions increase the chance of capturing nerves. Grade I, low level of certainty that larger
 lesions increase duration of pain relief).

 On the other hand, in the NPPG the treatment of the DRG with PRF should interrupts and
 possibly treat the intercellular and molecular circuits at the base of the central pain
 sensitization, improving the outcomes considered in this study.

 The biggest effort of this study will be the standardization of all the procedures, to allow
 the maximal reproducibility, in line with the latest recommendation in diagnosis and
 treatment of low back pain of facet joint origin stated by the CPG-ASRAPM and current best
 practice in radiofrequency denervation of the lumbar facet joints published by the British
 Pain Society (CBP-BPS).

 The theory that chronic LBP of FJ origin can be related to a central sensitization mechanism
 is a new investigation field, with no other studies yet exploring our treatment hypothesis.

 Therefore, it is important to carry out research projects that clarify which technical
 variables are those that provide an improvement in pain control and, above all, an
 improvement in the quality of life in these patients.

 Some of the conclusions of this project could be possible applied by professionals of the
 Pain Units worldwide in their daily activity, in order to provide our patients with the best
 care and the best possible results. It is a clinical study and therefore its translation to
 the clinical practice can be direct.

 TREATMENTS The application of radiofrequency (RF) signals to neural tissue is well
 established in the treatment of movement, mood, and chronic pain disorders. Undesired neural
 signals, such as those transmitting nociceptive pain, are interrupted when high-frequency
 current (100-1,000 kHz) flowing through an RF probe's active tip raises the temperature at a
 soma/ganglion or axon/nerve to destructive levels (45-50°C) by means of frictional heating.
 The process is known as RF heat lesioning, RF thermocoagulation, RF ablation, or thermal RF.
 The volume of tissue damaged by RF heating is called a heat lesion. Monopolar RF (the
 technique used in this hospital) refers to current flow between a probe electrode and a large
 area ground pad placed on the skin's surface. Bipolar RF refers to current flow between two
 probe electrodes without a ground pad.

 RF heat lesioning includes cooled RF, wherein the electrode is internally cooled by
 circulating fluid but surrounding tissue is exposed to destructive temperatures. Water-cooled
 radiofrequency (WCRF) ablation is a minimally invasive neuroablative technique used in the
 treatment of various pain syndromes. The mechanism of pain relief from WC-RF application is
 analogous to CRF application: a thermal lesion is created, by applying radiofrequency (RF)
 energy through an electrode placed in the vicinity of the target neural structure, with the
 aims of interrupting the afferent nociceptive pathways. The difference already mentioned is
 that the 'cooled' radiofrequency probes have water running through the probe tip, which keeps
 the tip cooled and allows a larger lesion to be made. Since the physician can't actually see
 the nerve he is trying to target, larger lesions should theoretically improve his chances of
 hitting it. The 'cooling' of the water also allows the temperatures to be lower than what is
 needed for standard RF (approximately 60°C).It is widely accepted that the PRF action
 mechanism (involving lower temperatures, below 42-44 °C) is most likely related to the
 induced electric field, rather than to thermal effects. Different effects of exposure to PRF
 electrical fields have already been reported. Some studies have revealed evidence of
 morphological changes in the neuronal cells after PRF treatment that affect the inner
 structures of axons. These structural changes consist of mitochondria swelling and disruption
 of the normal organisation of the microtubules and microfilaments that preferentially affect
 C-fibres and to a lesser extent Aδ fibres. In addition, transient ultrastructural changes
 such as endoneural oedema and collagen deposition have also been found. Besides structural
 changes, the effects on cellular activity and gene expression have also been observed as well
 as an increase in the expression of inflammatory proteins. All these effects could
 potentially inhibit the transmission of nerve signals through C-fibres, which would lead to
 pain relief.

 Number and laterality of medial branches to be lesioned is to be decided after a clinical
 examination by the pain physician. When selecting targets for blocks, levels should be
 determined based on clinical presentation, radiological findings when available, tenderness
 on palpation performed under fluoroscopy. A maximum of eight medial branches at a maximum of
 four vertebral levels may be lesioned in a single sitting, subjects with unilateral pain to
 receive unilateral treatment. A maximum of three DRG for each side will be treated in a
 single sitting.

 For various reasons, medial branch blocks are the only acceptable and validated diagnostic
 test as an indication for medial branch neurotomy. The paradigm of lumbar medial branch
 neurotomy is that patient's pain can be relieved by coagulating the nerves that mediate
 (transmit) their pain. An essential prerequisite, therefore, is that it must be shown that
 the target nerves are responsible for the patient's pain. This is achieved by controlled
 diagnostic blocks of the medial branches of the cervical and lumbar dorsal rami that mediate
 the pain. In order to reduce the likelihood of responses being false positive, controlled
 blocks are mandatory.

 An issue in this sense is represented by the relatively high percentage of false positive MBB
 for placebo effect (up to 30%) described in the literature (patients that responds positively
 to the MMB, but that fail or will possibly again fail a sustained benefit after the
 conventional procedure - control group). On the other side some patients may respond
 positively to the MBB but presents with a neuropathic back pain, possibly leading to a bias
 in selection, because in this case the mechanisms involved in the origin of back pain could
 be both neuropathic and nociceptive/mechanic in nature.

 Considering the high percentage of placebo related effect in the false positive group, the
 only way to exclude this kind of false positive is to perform a placebo-controlled
 pre-procedural MBB, where the placebo procedures will be difficult to be approved by any
 ethical committee, due to the relatively safety of this procedures.

 For this reasons this investigators decided to exclude patients positive to the MBB but with
 neuropathic pain and the patients with negative MBB and negative DN4 score.

 All the patients recruited in this study have been previously treated in our pain service by
 experienced interventionists anesthesiologists (this will suppose that the percentage of
 patients actually positive to the MBB because of previous inefficacy technique should be
 really low).

 Indeed, this study group decided to perform a single MBB with 0.5 mL of levo-bupivacaine 5
 mg/mL, that is the consensus preferred solution, under ultrasonographic guidance, in our
 technical operative room, with needle tip to be positioned on the curvature between the
 articular process and transverse process.

 Three radiofrequency techniques have been in use over the past three decades. The scientific
 community refers to them by name of continents where each was originally described: European,
 North American, and Australian.

 The technique described by Nath and all. and mentioned like standard of treatment in the last
 consensus on best practice in RFA of the lumbar facet join by the British Pain Society,
 similar to the Australian technique, is described as follows: the lumbar spine is visualized
 and the radiograph beam is adjusted to come from a posterior-lateral aspect to get the best
 possible view of the curvature of the medial part of the upper border of the transverse
 process where it ascends to become the ventral-lateral border of the superior articular
 process. In patients with a hypertrophic superior articular process due to arthritic changes
 greater lateral rotation can be required. The C-arm is then inclined caudal so that the
 direction of the radiograph beam is from upwards looking below and somewhat medially along
 the groove in which the medial branch lies.

 A 22 SWG SMK C15 cannula with a 5 mm active tip is introduced along the direction of the
 radiograph beam, in the so-called "tunnel technique" until bone contact is made with the
 lower part of the transverse process (L5 and higher). The cannula is then rotated so that the
 bevel was against the bone allowing the needle to slide up in the groove maintaining contact
 with the bone surface till the tip was at the upper border and in the centre of the curvature
 formed by the upper border of the transverse process ascending to form the lateral border of
 the articular process. The position is then checked in the tunnel view, the postero-lateral
 view as well as a cephalad view. The lateral view confirms that the cannula is not too far
 in, encroaching on the foramen.

 At the S1 level (L5 dorsal ramus) a similar view is maintained to lay the cannula in the
 groove between the lower part of the lateral aspect of the superior articular process of S1
 and the upper surface of the ala of the sacrum. The tunnel view confirms the position in the
 groove. The forward advance is checked rotating the C-arm to look from a more lateral aspect
 to visualize the anterior border of the superior articular process of S1, and then from a
 more cephalad aspect to visualize the point of the needle in relation to the anterior border
 of the ala of the sacrum.

 About the DRG, the radiological location can be divided into 3 types-the intraspinal,
 foraminal, and extraforaminal regions; most DRG neurons are of the foraminal type. This
 position corresponds to the dorsal-cranial quadrant of the intervertebral foramen on the
 lateral view in fluoroscopy, and the middle of the pedicle column on the anteroposterior (AP)
 view. However, if the arthritic degenerative changes and foraminal stenosis are severe,
 positioning the needle to target the DRG on fluoroscopy may be difficult. Accordingly, needle
 tips can be placed laterally on the side of the corresponding pedicle in the AP view. When
 the RF needle is close to the target position, the stylet of the RF needle is removed, and
 the RF probe is inserted. Similar to the Australian technique, the C-arm is placed with a
 20-30° lateral tilt on the side to treat, with a slightly caudocephalad tilt, to better
 visualize the foramen, just under the inferior border of the transvers process, with
 placement of the needle in tunnel vision. The final position of the RF probe is determined
 with sensory stimulation (50 Hz), at a voltage below 0.5 V. Proximity of the needle to the
 DRG is determined by appropriate sensory stimulation with 50 Hz (0.4-0.6 V), when the patient
 feels a tingling sensation. If the threshold value exceeded 0.5V, the needle is carefully
 advanced until the patient feels sensory stimulation. Motor stimulation at 2 Hz is used to
 determine a threshold 1.5-2.0 times greater than the sensory threshold to avoid placement
 near the anterior nerve root and perform the procedure safely. Contrast injection at the end
 of the needle tip positioning could represent a further confirmation.

 Despite the fact that a curved cannula could increase the size of the lesion, a straight
 22-gauge cannula with a 5-mm active tip remains the tool most commonly used for
 radiofrequency denervation of the facet nerves, and it will be the used cannula in the CRF
 group and in the DRG-PRF group. A 4-mm active tip 10 cm long 17G cannula will be placed for
 WCRF.

 This group of investigation will adopt a modified Nath technique (using a 5 to 15 degree
 cephalo-caudal inclination and a needle view similar to that obtained with the advanced
 Australian technique), for CRF and WCRF ablation of MBDR.

 Position of the radiofrequency cannula will be confirmed by fluoroscopy with AP, oblique, and
 lateral view. Once the cannula(e) position is confirmed, routine motor testing will be
 carried out with a threshold for lower limb muscle contraction of 2V. Lower limb muscle
 contractions occurring below the threshold will prompt a repositioning of the RF cannula.
 Sensory stimulation will be applied when single lesions are anticipated (CRF groups); sensory
 stimulation of 0,6V mean that the needle is placed at less than 3 mm from the MBDR, that is
 the ideal distance to realize an adequate lesion. When multiple or large lesions are planned,
 the evidence for sensory stimulation is inconclusive; despite this fact, it was decided to
 check for sensory stimulation for all patients involved in this study, knowing that in the
 WCRF and CRF groups such stimulation could be inconclusive.

 Due to the larger expected lesion size in the WCRF, like suggested by the work of Malik et
 all. the investigators will ensure a "safe distance" from the segmental spinal nerve by
 adopting the following safety measures: (a) the electrode tip will be placed on the
 transverse process, about 4 mm lateral to its junction with the superior articular process;
 (b) the parameters used for sensory testing will be modified and paresthesia will be sought
 at > 0.6 V, between 0.8 V to 1.0 V.

 In the case of CRF and WCRF before starting the treatment, 1 ml of lidocaine 1% will be
 injected through the cannula.

 Each lesion will be carried out at 80° C for 90 seconds in the CRF group. One lesions will be
 applied for each treated level.

 Each lesion in the WCRF group will be carried out at 60° C for 150 seconds. One lesion will
 be applied for each treated level.

 At the end of the procedure 1 to 1.5 ml of a mixture of ropivacaine 0,2% 8ml + betamethasone
 11.8 mg 2ml will be injected before the extraction of the needle, in both this groups.

 In the case of DRG-PRF, a pulsed current (20ms, 2 Hz) is applied (1 time for 120 seconds),
 with a 45V output, 20ms lasting impulse (480ms pause). During this procedure, the temperature
 at the tip of the electrode is not supposed to exceed 42℃.

 At the end of the procedure, 0,5 to 1 ml of a mixture of ropivacaine 0,1% 8ml and
 dexamethasone 8mg will be injected before needle extraction.

 The CRF treatment and the DRG-PRF will be realized with the Cosman G4 Radiofrequency
 Generator. For the WCRF a COOLED RF Generator of Halyard will be used. All the procedures can
 be performed in day hospital, with no need for hospitalization.

 Ones the needle is positioned, the wire is retired and the probe is inserted; the measured
 impedance has to be between 200 and 700Ω to confirm the proximity to the target structure.

 All patients will be in a prone position.
Inclusion Criteria:

 -  patients with chronic lumbar back pain supposed to be of facet joint origin (low back
 pain irradiated to buttocks, legs, eventually feet in absence of exclusion criteria);

 -  positivity to FJ provocative clinical tests, possible muscle spasm over the affected
 joints;

 -  positivity to DN4 assessment in the NPPG + negative MBB and negative DN4 assessment +
 positive MMB in the NMPG;

 -  efficacy of MBDR-RF treatment for at least one time reported in the personal clinical
 history, unresponsive to the last CRF or WCRF (only for the NPPG);

 -  an MRI no more than 2 years;

 -  basal NRS ≥ 7;

 -  patients between 18y and 85y;

 -  ASA (American Society of Anaesthesiologists scale) I-III;

 -  absence of severe chronic disease associated, full mental capacity to sign the
 informed consent.

 This group is well aware that nowadays literature lack of confirmed clinical diagnostic
 criteria, like underlined in the last CPG-ASRAPM. Despite this issue, we decided to select
 our clinical criteria to better identify LBP of FJ origin following some of the indications
 mentioned in the Delphi survey of an expert panel (Wilde et al., 2007):

 -  reproduction of similar or even worsening of basal pain during paravertebral finger
 pressure applied no more than 2-3 cm laterally to the midline (89% expert acceptance);

 -  improvement of patient's pain during the flexion of the trunk while sitting (78%
 expert acceptance);

 -  reduced range of motion or increased stiffness during local lateral passive movements
 (61% expert acceptance);

 -  positive balance test with increased pain during extension - stress movements (after
 the flexion manoeuvre), or during lateral flexion (starting from 20 degree) and
 rotational axial movements (56% expert acceptance).

 -  Another manoeuvre, taking into consideration the spinal columns' biomechanics, is
 realized asking the patients while standing with joined feet, to flex completely the
 trunk trying to touch with hands the top of his feet; this movement should not provoke
 patients' usual pain or worsen it; after that is invited to slowly return to a neutral
 position, stopping for 5 seconds in a 90-degree position between the trunk and the
 feet; during the extension movement to recover the initial position, the pain could
 worsen, or mimic the patients' usual pain, but it can't improve.

 We decided to include also patient that present with bilateral low back pain, despite this
 survey describe localized unilateral low back pain like one of possible clinical indicator
 of lumbar facet joint pain (80% expert agreement); this decision is based on our clinical
 experience.

 Exclusion Criteria:

 -  positive MBB with positive DN4;

 -  negative MMB with negative DN4;

 -  positive EMG for neuropathic pain of radicular origin (89% expert acceptance),

 -  diagnostic imaging of significant radicular compression (based on the radiologist
 judgement);

 -  late diagnosis of other causes of LBP, cancer related pain, neoplastic patients,
 patients with life expectation inferior to 1 year;

 -  BMI > 35;

 -  patients insurance or work absence related interests

 -  patient refusal

 -  Back's depression inventory II (BDI-II) > 20,

 -  previous lumbar spinal, pelvic and knee surgery, or significant stenosis of the spinal
 canal that can interfere with diagnosis;

 -  patient with systemic infection, pregnant or breastfeeding woman, untreatable
 coagulative problems;

 -  clinical doubt by the enrolling physician that can interfere with the evaluation's
 efficacy of the procedures under investigation (like hip pain, cluneal nerve's
 entrapment pain, trochanteritis, myofascial pain, etc.);

 -  any contraindication to neuraxial injection.

 -  Social risk factors that could influence the adherence to the study protocol will be
 taken into consideration and valuated accordingly.