BackgroundOsteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark.ResultsPEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam.ConclusionThe present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

Background: Previous functional MRI studies have revealed that ongoing clinical pain in different chronic pain syndromes is directly correlated to the connectivity strength of the resting default mode network (DMN) with the insula. Here, we investigated seed-based resting state DMN-insula connectivity during acute migraine headaches. Methods: Thirteen migraine without aura patients (MI) underwent 3 T MRI scans during the initial six hours of a spontaneous migraine attack, and were compared to a group of 19 healthy volunteers (HV). We evaluated headache intensity with a visual analogue scale and collected seed-based MRI resting state data in the four core regions of the DMN: Medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs), as well as in bilateral insula. Results: Compared to HV, MI patients showed stronger functional connectivity between MPFC and PCC, and between MPFC and bilateral insula. During migraine attacks, the strength of MPFC-to-insula connectivity was negatively correlated with pain intensity. Conclusion: We show that greater subjective intensity of pain during a migraine attack is associated with proportionally weaker DMN-insula connectivity. This is at variance with other chronic extra-cephalic pain disorders where the opposite was found, and may thus be a hallmark of acute migraine head pain.

We hypothesize that abnormal migraine cycle-dependent dynamics of connectivity between subcortical and cortical excitation/inhibition networks may contribute to clinical features of MO and recurrence of attacks.

BackgroundHere, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine.MethodsEighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs.ResultsAfter 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks.ConclusionsKD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.

The objectives of this paper are to evaluate the efficacy and tolerability of topiramate, given at the dose of 100 mg/day, in the prophylactic treatment of migraine. The hypothesis that migraine is the result of a condition of neuronal hyperexcitability and the quest for drugs that are able to limit the number of crises justifies the attempt to utilise the new antiepileptic drugs in the prophylaxis of this pathology, which is so important due to its high prevalence and due to the high disability it causes. The study was randomised double-blind versus placebo, lasting 16 weeks, and was preceded by a run-in period of 4 weeks. One hundred and fifteen patients were randomly allocated to treatment with topiramate (TPM) or placebo: 35 patients completed the study in the TPM group and 37 patients in the placebo group. At the end of the double-blind phase of study, in the TPM group, we recorded a significant reduction in the frequency of migraine crises (from 5.26 at baseline to 2.60 in the last 4 weeks), a significant reduction in the quantity of symptomatic drugs taken as compared to the placebo control group (from 6.17+/-1.80 SD to 2.57+/-0.80) and a significant downward trend in the number of days of disability over the 16-week period of therapy. In the TPM group, side effects were transient and well tolerated. TPM has thus proven its efficacy and tolerability in the prophylaxis of migraine.