A systematic review was conducted to identify and summarize the available scientific literature addressing pressure pain threshold (PPT) values over the temporalis, masseter, and frontalis muscles in healthy humans, patients with tension-type headache (TTH), and those with migraine both in males and females. Six relevant medical databases for the literature search were included: PubMed, Web of Science, Cochrane, CINAHL, BioMed Central, and Embase. The search strategy was performed applying 15 keywords (eg, pressure pain threshold, temporalis muscle, tension type headache, pressure algometer) and their combinations. A total of 156 articles were identified, and 40 relevant articles were included. The main outcomes of the systematic review were extracted, and it was demonstrated that the PPT values in general were lower in patients compared with healthy subjects, and this was especially noted for temporalis in both females (migraine: 231.2 ± 38.3 kPa < TTH: 248.4 ± 39.3 kPa < healthy: 282.1 ± 70.8 kPa) and males (migraine: 225.5 ± 61.2 kPa < TTH: 264.2 ± 32.5 kPa < healthy: 314.8 ± 63.3 kPa). The masseter muscle seemed to be more sensitive than the other 2 muscles, in both females (healthy: masseter 194.1 ± 62.7 kPa < frontalis 277.5 ± 51.1 kPa < temporalis 282.1 ± 70.8 kPa) and males (healthy: masseter 248.2 ± 48.4 kPa < temporalis 314.8 ± 63.3 < frontalis 388 kPa). Females had lower PPT values than those of males in temporalis, masseter, and frontalis muscles. This work is the first to systematically review the scientific literature addressing PPT values over craniofacial muscles of healthy subjects, patients with TTH, and those with migraine to provide the PPT value ranges. Based on these findings, a set of guidelines was established to assist future studies including PPT assessments over craniofacial muscles.

The post-transcriptional regulator molecules, microRNAs, have emerged as important biomarkers and modulators of numerous pathophysiological processes including oncogenesis and cardiovascular diseases. Recently, a significant number of dysregulations in microRNAs have been reported in patients suffering from painful disorders such as complex regional pain syndrome, cystitis-induced chronic pain and irritable bowel disorder, in both affected tissues and the circulation. Moreover, microRNAs are known to be involved in pain processing based on several recent findings in animal models of inflammatory and neuropathic pain. The basis of this review was to cover and summarize available articles in English encompassing "microRNA and pain". In animal pain models widespread microRNA modulation is present and manifests on multiple levels i.e.: the dorsal root ganglia, the spinal dorsal horn and the brain. Numerous functional in vivo studies have found that dysregulated microRNAs are involved in the post-transcriptional modulation of genes implicated in pain generation and maintenance. Lastly, a few animal studies have delivered promising results as to the possibility of applying microRNAs as therapeutics to alleviate established pain and several clinical studies have highlighted the potential in applying microRNAs as biomarkers in painful conditions such as complex regional pain syndrome and fibromyalgia. This review briefly introduces the basics of microRNAs, their biogenesis and function, and mainly focuses on the recent advances made in understanding the role of microRNAs in relation to pain processing and painful conditions. It also provides an overview of widely diverse methodological approaches and results with a potential for future implications of microRNAs in the diagnosis and treatment of pain.

The present human study aimed at investigating the effect of subcutaneous administration of Botulinum toxin type A (BoNT/A) on capsaicin-induced trigeminal pain, neurogenic inflammation and experimentally induced cutaneous pain modalities. Fourteen healthy males (26.3+/-2.6 years) were included in this double-blind and placebo-controlled trial. The subjects received subcutaneous BoNT/A (22.5U) and isotonic saline in the mirror sides of their forehead. Pain and neurogenic inflammation was induced by four intradermal injections of capsaicin (100mug/muL) (before, and days 1, 3 and 7 after treatments). The capsaicin-induced pain intensity, pain area, the area of secondary hyperalgesia, the area of visible flare and vasomotor reactions were recorded together with cutaneous heat, electrical and pressure pain thresholds. BoNT/A reduced the capsaicin-induced trigeminal pain intensity compared to saline (F=37.9, P<0.001). The perceived pain area was smaller for the BoNT/A-treated side compared to saline (F=7.8, P<0.05). BoNT/A reduced the capsaicin-induced secondary hyperalgesia (F=5.3, P<0.05) and flare area (F=10.3, P<0.01) compared to saline. BoNT/A reduced blood flow (F(1,26)=109.5, P<0.001) and skin temperature (F(1,26)=63.1, P<0.001) at the capsaicin injection sites compared to saline and its suppressive effect was maximal at days 3 and 7 (P<0.05, post hoc test). BoNT/A elevated cutaneous heat pain thresholds (F=17.1, P<0.001) compared to saline; however, no alteration was recorded for electrical or pressure pain thresholds (P>0.05). Findings from the present study suggest that BoNT/A appears to preferentially target Cfibers and probably TRPV1-receptors, block neurotransmitter release and subsequently reduce pain, neurogenic inflammation and cutaneous heat pain threshold.

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