Pain
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Pain and other sensory signs in patients with restless legs syndrome (RLS) are still poorly understood, as most investigations focus on motor system dysfunctions. This study aimed to investigate somatosensory changes in patients with primary RLS and the restoration of somatosensory function by guideline-based treatment. Forty previously untreated RLS patients were investigated unilaterally over hand and foot using quantitative sensory testing (QST) and were compared with 40 age- and gender-matched healthy subjects. ⋯ QST suggested a type of spinal or supraspinal central sensitization differing from neuropathic pain or human experimental models of central sensitization by the absence of dynamic mechanical allodynia. Reversal of pinprick hyperalgesia by l-DOPA may be explained by impaired descending inhibitory dopaminergic control on spinal nociceptive neurons. Restoration of tactile sensitivity and paradoxical heat sensations suggest that they were functional disturbances resulting from central disinhibition.
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Endogenous TRPV1 agonists such as oxidized linoleic acid metabolites (OLAMs) and the enzymes releasing them [eg, cytochrome P450 (CYP)] are up-regulated after inflammation in the rat. However, it is not known whether such agonists are elevated in human inflammatory pain conditions. Because TRPV1 is expressed in human dental pulp nociceptors, we hypothesized that OLAM-CYP machinery is active in this tissue type and is increased under painful inflammatory conditions such as irreversible pulpitis (IP). ⋯ These data suggest that LA metabolites produced in human inflamed tissues act as TRPV1 agonists and that the metabolite production can be targeted by CYP inhibition. In addition, immunohistochemical analysis of 2 CYP isoforms, CYP2J and CYP3A1, were shown to be predominately expressed in immune cells infiltrating the inflamed dental pulp, emphasizing the paracrine role of CYP enzymes in OLAM regulation. Collectively, our data indicate that the machinery responsible for OLAM production is up-regulated during inflammation and can be targeted to develop potential analgesics for inflammatory-induced dental pain.
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Randomized Controlled Trial Multicenter Study
The efficacy of a glial inhibitor, minocycline, for preventing persistent pain after lumbar discectomy: a randomized, double-blind, controlled study.
Minocycline strongly inhibits microglial activation, which contributes to central sensitization, a major mechanism underlying chronic pain development. We hypothesized that the perioperative administration of minocycline might decrease persistent pain after lumbar discectomy. We randomly assigned 100 patients undergoing scheduled lumbar discectomy to placebo and minocycline groups. ⋯ The incidence and intensity of neuropathic pain and functional scores did not differ between the minocycline and placebo groups. Exploratory analysis suggested that minocycline might be effective in a subgroup of patients with predominantly deep spontaneous pain at baseline. Perioperative minocycline administration for 8 days does not improve persistent pain after lumbar discectomy.
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This study investigated whether one becomes more quickly aware of innocuous somatosensory signals at locations of the body where pain is anticipated. Undergraduate students (N=20) indicated which of 2 stimuli that were administered to each hand using a range of stimulus onset asynchronies (SOAs), was presented first. Participants were instructed that the color of a cue (1 of 2 colors) signaled the possible occurrence of pain on 1 hand (threat trials). ⋯ Results showed that during threat trials tactile stimuli on the hand where pain was expected, were perceived earlier in time than stimuli on the "neutral" hand. These findings demonstrate that the anticipation of pain at a particular location of the body resulted in the prioritization in time of somatosensory sensations at that location, indicating biased attention towards the threatened body part. The value of this study for investigating hypervigilance for somatosensory signals in clinical populations such as patients with chronic lower back pain is discussed.
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We conducted a postal survey to assess the prevalence and characteristics of neuropathic pain and migraine in a cohort of multiple sclerosis (MS) patients. Of the 1300 questionnaires sent, 673 could be used for statistical analysis. Among the respondents, the overall pain prevalence in the previous month was 79%, with 51% experiencing pain with neuropathic characteristics (NCs) and 46% migraine. ⋯ Migraine, but not NC pain, was associated with age, disease duration, relapsing-remitting course, and interferon-beta treatment. This suggests that NC pain and migraine are mediated by different mechanisms. Therefore, pain mechanisms that specifically operate in MS patients need to be characterized to design optimal treatments for these individuals.