A subgroup of patients that undergo TKR surgery have evidence of neuropathic pain and central sensitization that may predispose to severe postoperative pain. This study assesses the correlation of MRI detected bone marrow lesions (BMLs) and synovitis with markers of neuropathic pain and central sensitization in patients undergoing TKR surgery and healthy volunteers. 31 patients awaiting TKR and 5 healthy volunteers were recruited. Each subject underwent a 3-T knee MRI scan that was graded for BMLs (0–45) and synovitis (0–3) using subsets of the MRI Osteoarthritis Knee Score (MOAKS). All subjects were asked to complete the PainDetect questionnaire to identify nociceptive pain (< 13), unclear pain (13–18) and neuropathic pain (>18). Correlation between BMLs and PainDetect score was the primary outcome measure. Secondary outcomes included the correlation of synovitis to PainDetect and temporal summation (TS) a measure of central sensitization to the PainDetect score. TS was determined using a monofilament to evoke pain. Pilot histological analysis of the prevalence of osteoclasts (TRAP. +. ) within BMLs versus normal subchondral bone was performed, implying a role in BML pathology. Increasing BML MOAKS score correlated with neuropathic pain (painDetect), r. s. = 0.38, p=0.013 (one-tailed). There was a positive correlation between synovitis and PainDetect score, τ =0.23, p= 0.031 (one-tailed). TS was greater in the neuropathic pain than in nociceptive pain patients, U = 18.0, p=0.003 (one-tailed). TRAP staining identified more osteoclasts within BMLs than contralateral condyle lesion free subchondral bone, z = −2.232, p = 0.026 (Wilcoxon Signed Rank Test, one-tailed). BMLs and synovitis are more prevalent in neuropathic pain and central sensitization in knee OA. Higher osteoclast prevalence was seen within BMLs which may help explain the association with BMLs and pain in OA

Background. Charcot neuropathic osteoarthropathy is a rare, destructive process affecting the bones and joints of feet in patients with diabetic peripheral neuropathy. The aetiology of Charcot remains unknown, although it has been suggested that it is triggered by the occurrence of inflammation in the foot of a susceptible individual, and that the inflammation results in increased osteoclastic activity. Hypothesis. The increased bone turnover in acute Charcot is associated with increased concentrations of pro-inflammatory cytokines, related signalling peptides and bone turnover markers. Methods. 17 patients newly presenting with acute Charcot in diabetes and 16 non-diabetic patients without neuropathy undergoing elective forefoot surgery provided informed consented to participate. Samples of bone were taken by needle biopsy, and were stained with H&E to determine bone architecture and bone remodelling. Serum ALP, CTX, OPG and sRANKL TNF, IL1-beta, IL6 and CRP were measured by immunoassay. Blood was taken from the dorsal foot vein of both the affected and the unaffected foot, as well as an antecubital vein. Results. Classic histopathology features of fracture and bone remodelling were evident in Charcot bone biopsies. Systemic circulating concentrations in the Charcot group antecubital vein for both IL6 and OPG were significantly greater than in controls (p<0.05). There were no significant differences between the dorsal vein concentrations of any analyte when the affected and unaffected feet were compared. However, in patients with an acute Charcot foot the concentration of OPG, ALP and CTX was higher in sera from the dorsal vein of affected foot when compared to controls (p<0.05), this difference was highly significant for IL6 (p<0.001). Conclusion. The elevation in CTX observed in the affected foot in patients with an acute Charcot foot reflects the bone breakdown and remodelling which is present. The higher circulating concentration of IL-6 in the Charcot patient group, reflects the inflammation which is present and which is thought to be central to the development of the condition. Although OPG values were significantly greater in Charcot than control group, circulating concentrations of OPG are known to be higher in diabetes

A major cause of morbidity in lower limb amputees is phantom limb pain (PLP) and residual limb pain (RLP). This study aimed to determine if surgical interposition of nerve endings into adjacent muscle bellies at the time of major lower limb amputation can decrease the incidence and severity of PLP and RLP.

Data was retrospectively collected from January 2015 to January 2021, including eight patients that underwent nerve interposition (NI) and 36 that received standard treatment. Primary outcomes included the 11-point Numerical Rating Scale (NRS) for pain severity, and Patient-Reported Outcomes Measurement Information System (PROMIS) pain intensity, behaviour, and interference. Secondary outcome included Neuro-QoL Lower Extremity Function assessing mobility. Cumulative scores were transformed to standardised t scores.

Across all primary and secondary outcomes, NI patients had lower PLP and RLP. Mean ‘worst pain’ score was 3.5 out of 10 for PLP in the NI cohort, compared to 4.89 in the control cohort (p=0.298), and 2.6 out of 10 for RLP in the NI cohort, compared to 4.44 in the control cohort (p=0.035). Mean ‘best pain’ and ‘current pain’ scores were also superior in the NI cohort for PLP (p=0.003, p=0.022), and RLP (p=0.018, p=0.134).

Mean PROMIS t scores were lower for the NI cohort for RLP (40.1 vs 49.4 for pain intensity; p=0.014, 44.4 vs 48.2 for pain interference; p=0.085, 42.5 vs 49.9 for pain behaviour; p=0.025). Mean PROMIS t scores were also lower for the NI cohort for PLP (42.5 vs 52.7 for pain intensity; p=0.018); 45.0 vs 51.5 for pain interference; p=0.015, 46.3 vs 51.1 for pain behaviour; p=0.569). Mean Neuro-QoL t score was lower in NI cohort (45.4 vs 41.9;p=0.03).

Surgical interposition of nerve endings during lower limb amputation is a simple yet effective way of minimising PLP and RLP, improving patients’ subsequent quality of life. Additional comparisons with targeted muscle reinnervation should be performed to determine the optimal treatment option.

Differences at motor control strategies to provide dynamic balance in various tasks in diabetic polyneuropatic (DPN) patients due to losing the lower extremity somatosensory information were reported in the literature. It has been stated that dynamics of center of mass (CoM) is controlled by center of pressure (CoP) during human upright standing and active daily movements. Indeed analyzing kinematic trajectories of joints unveil motor control strategies stabilizing CoM. Nevertheless, we hypothesized that imbalance disorders/CoM destabilization observed at DPN patients due to lack of tactile information about the base of support cannot be explained only by looking at joint kinematics, rather functional foot usage is proposed to be an important counterpart at controlling CoM.

In this study, we included 14 DPN patients, who are diagnosed through clinical examination and electroneuromyography, and age matched 14 healthy subjects (HS) to identify control strategies in functional reach test (FRT). After measuring participants’ foot arch index (FAI) by a custom-made archmeter, they were tested by using a force plate, motion analysis system, surface electromyography and pressure pad, all working in synchronous during FRT. We analyzed data to determine effect of structural and functional foot pathologies due to neuropathy on patient performance and postural control estimating FAI, reach length (FR), FR to height (H) ratio (FR/H; normalized FR with respect to height), displacement of CoM and CoP in anteroposterior direction only, moment arm (MA, defined as the difference between CoP and CoM at the end of FRT), ankle, knee and hip joint angles computed at the sagittal plane for both extremities. Kinematic metrics included initial and final joint angles, defined with respect to start and end of reaching respectively. Further difference in the final and initial joint angles was defined as Δ.

FAI was founded significantly lower in DPN patients (DPN: 0.3404; HS: 0.3643, p= <0.05). The patients’ FR, FR/H and absolute MA and displacement of CoM were significantly shorter than the control group (p= <0.05). Displacement of CoP between the two groups were not significant. Further we observed that CoM was lacking CoP in DPN patients (mean MA: +0.88 cm), while leading CoP in HS (mean MA: −1.59 cm) at the end of FRT. All initial angles were similar in two groups, however in DPN patients final right and left hip flexion angle (p=0.016 and p=0.028 respectively) and left ankle plantar flexion angle (p=0.04) were smaller than HS significantly. DPN patients had significantly less (p=0.029) hip flexion (mean at right hip angle, Δ=25.0°) compared to HS (Δ=33.53°) and ankle plantar flexion (DPN mean at right ankle angle, Δ=6.42°, HS mean Δ=9.07°; p=0.05).

The results suggest that movement of both hip and ankle joints was limited simultaneously in DPN patients causing lack of CoM with respect to CoP at the end of reaching with significantly lower FAI. These results lead to the fact that cutaneous and joint somatosensory information from foot and ankle along with the structure of foot arch may play an important role in maintaining dynamic balance and performance of environmental context. In further studies, we expect to show that difference at control strategies in DPN patients due to restricted functional foot usage might be a good predictor of how neuropathy evolves to change biomechanical aspects of biped erect posture.

Objectives

Acetabular retractors have been implicated in damage to the femoral and obturator nerves during total hip replacement. The aim of this study was to determine the anatomical relationship between retractor placement and these nerves.

A rat model of lumbar root constriction with an additional sympathectomy in some animals was used to assess whether the sympathetic nerves influenced radicular pain. Behavioural tests were undertaken before and after the operation.

On the 28th post-operative day, both dorsal root ganglia and the spinal roots of L4 and L5 were removed, frozen and sectioned on a cryostat (8 μm to 10 μm). Immunostaining was then performed with antibodies to tyrosine hydroxylase (TH) according to the Avidin Biotin Complex method. In order to quantify the presence of sympathetic nerve fibres, we counted TH-immunoreactive fibres in the dorsal root ganglia using a light microscope equipped with a micrometer graticule (10 x 10 squares, 500 mm x 500 mm). We counted the squares of the graticule which contained TH-immunoreactive fibres for each of five randomly-selected sections of the dorsal root ganglia.

The root constriction group showed mechanical allodynia and thermal hyperalgesia. In this group, TH-immunoreactive fibres were abundant in the ipsilateral dorsal root ganglia at L5 and L4 compared with the opposite side. In the sympathectomy group, mechanical hypersensitivity was attenuated significantly.

We consider that the sympathetic nervous system plays an important role in the generation of radicular pain.

Using a rat model the characteristics of the sensory neurones of the dorsal-root ganglia (DRG) innervating the hip were investigated by retrograde neurotransport and immunohistochemistry.

Fluoro-Gold solution (FG) was injected into the left hip of ten rats. Seven days later the DRG from both sides between T12 and L6 were harvested. The number of FG-labelled calcitonin gene-related peptide-immunoreactive or isolectin B4-binding neurones were counted.

The FG-labelled neurones were distributed throughout the left DRGs between T13 and L5, primarily at L2, L3, and L4. Few FG-labelled isolectin B4-binding neurones were present in the DRGs of either side between T13 and L5, but calcitonin gene-related peptide-immunoreactive neurones made up 30% of all FG-labelled neurones.

Our findings may explain the referral of pain from the hip to the thigh or lower leg corresponding to the L2, L3 and L4 levels. Since most neurones are calcitonin gene-related peptide-immunoreactive peptide-containing neurones, they may have a more significant role in the perception of pain in the hip as peptidergic DRG neurones.