Human Studies

Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) is increasingly being investigated as a means of alleviating chronic pain. However, rTMS interventions are typically initiated once pain has already become chronic and maladaptive patterns of neural activity are likely to have been established. A critical question is whether M1 rTMS applied soon after pain onset can prevent the development of maladaptive neural activity and promote recovery. This study investigated the effect of 5 consecutive days of excitatory M1 rTMS on pain, functional limitation, mechanical hyperalgesia, descending inhibitory pain control, and M1 organisation in the transition from acute to sustained pain. Thirty healthy participants attended 8 sessions over a 16-day period. On Days 0, 2, and 4, nerve growth factor was injected into the right forearm to induce progressively developing muscle soreness and mechanical hyperalgesia. Active or sham excitatory rTMS was delivered on Days 4-8. Clinical and neurophysiological outcomes were recorded on Days 0, 2, 4, 6, 8, 11 and 14. Active rTMS promoted recovery of muscle soreness, pain, and mechanical hyperalgesia when compared to sham rTMS (all between-group p < 0.05). Corticomotor excitability and descending inhibitory pain control did not differ between groups. These findings suggest that active excitatory M1 rTMS promotes recovery of muscle soreness, pain, and mechanical hyperalgesia in the transition from acute to sustained experimental pain. The analgesic effects of M1 rTMS do not appear to be modulated by descending inhibitory pain control or local changes in corticomotor excitability.

The primary objective was to investigate the prevalence of neuropathic-like pain in patients with psoriatic arthritis (PsA). Secondary outcomes were to investigate whether mood, fatigue, pain, disease severity and fibromyalgia are associated with neuropathic-like pain in PsA patients.

The endogenous metabolite methylglyoxal (MG) accumulates in diabetic patients with neuropathic pain. MG could be a mediator of diabetes-induced neuropathic pain via TRPA1 activation and sensitization of the voltage-gated sodium channel subtype 1.8. In this study, we tested the algogenic and sensitizing effect of MG in healthy human subjects using intracutaneous microinjections. The involvement of C-fibers was assessed via selective A-fiber nerve block, axon-reflex-erythema and via single nerve fiber recordings in humans (microneurography). Involvement of the transduction channels TRPA1 and TRPV1 in MG-induced pain sensation was investigated with specific ion channel blockers. We showed for the first time in healthy humans that MG induces pain, axon-reflex-erythema and long-lasting hyperalgesia via the activation of C-nociceptors. Predominantly the subclass of mechano-insensitive C-fibers is activated by MG. A-fibers contribute only negligibly to the burning pain sensation. Selective harmacological blockade of TRPA1 or TRPV1 showed that TRPA1 is crucially involved in MG-induced chemical pain sensation and heat hyperalgesia. In conclusion, the ctions of MG via TRPA1 activation on predominantly mechanoinsensitive C-fibers might be involved in spontaneously perceived pain in diabetic neuropathy and hyperalgesia as well as allodynia.

The aim of this study was to determine if a preoperative pain neuroscience education program would result in superior outcomes compared to usual preoperative education for total knee arthroplasty.

Spinal cord stimulation (SCS) applied between T8 and T11 segments has been shown to be effective for the treatment of chronic pain of the lower back and limbs. However, the mechanism of the analgesic effect at these medullary levels remains unclear. Numerous studies relate glial cells with development and maintenance of chronic neuropathic pain. Glial cells are electrically excitable, which makes them a potential therapeutic target using SCS. The aim of this study is to report glia to neuron ratio in thoracic segments relevant to SCS, as well as to characterize the glia cell population at these levels. Dissections from gray and white matter of posterior spinal cord segments (T8, T9, intersection T9/T10, T10 and T11) were obtained from 11 human cadavers for histological analyses. Neuronal bodies and glial cells (microglia, astrocytes and oligodendrocytes) were immunostained, microphotographed and counted using image analysis software. Statistical analyses were carried out to establish significant differences of neuronal and glial populations among the selected segments, between the glial cells in a segment, and glial cells in white and gray matter. Results show that glia to neuron ratio in the posterior gray matter of the human spinal cord within the T8-T11 vertebral region is in the range 11 : 1 to 13 : 1, although not significantly different among vertebral segments. Glia cells are more abundant in gray matter than in white matter, whereas astrocytes and oligodendrocytes are more abundant than microglia (40 : 40 : 20). Interestingly, the population of oligodendrocytes in the T9/T10 intersection is significantly larger than in any other segment. In conclusion, glial cells are the predominant bodies in the posterior gray and white matter of the T8-T11 segments of the human spinal cord. Given the crucial role of glial cells in the development and maintenance of neuropathic pain, and their electrophysiological characteristics, anatomical determination of the ratio of different cell populations in spinal segments commonly exposed to SCS is fundamental to understand fully the biological effects observed with this therapy.