Objective Opioids have relieved more human suffering than any other medication, but their use is still fraught with significant concerns of misuse, abuse, and addiction. This theoretical article explores the hypothesis that opioid misuse in the context of pain management produces a hypersensitivity to emotional distress, termed hyperkatifeia. Results In the misuse of opioids, neural substrates that mediate positive emotional states (brain reward systems) are compromised, and substrates mediating negative emotional states (brain stress systems) are enhanced. A reflection and early marker of such a nonhomeostatic state may be the development of opioid-induced hyperkatifeia, defined as the increased intensity of the constellation of negative emotional/motivational symptoms and signs observed during withdrawal from drugs of abuse (derived from the Greek “katifeia” for dejection or negative emotional state) and is most likely to occur in subjects in whom the opioid produces a break with homeostasis and less likely to occur when the opioid is restoring homeostasis, such as in effective pain treatment. When the opioid appropriately relieves pain, opponent processes are not engaged. However, if the opioid is administered in excess of need because of overdose, pharmacokinetic variables, or treating an individual without pain, then the body will react to that perturbation by engaging opponent processes in the domains of both pain (hyperalgesia) and negative emotional states (hyperkatifeia). Conclusions Repeated engagement of opponent processes without time for the brain’s emotional systems to reestablish homeostasis will further drive changes in emotional processes that may produce opioid abuse or addiction, particularly in individuals with genetic or environmental vulnerability.

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Longitudinal melanonychia striata, presenting as a black linear vertical band of the nail plate, can be caused by pigmented lesions and non-pigmented etiologies. A fungal infection of the nail plate, also referred to as onychomycosis or tinea unguim, can result from dermatophytes, non-dermatophyte molds, and Candida . Albeit rare, Candida -associated fungal melanonychia can present as a longitudinal black nail plate streak. The case of a 79-year-old man who developed a solitary linear black streak on his right fourth fingernail after a prior history of recent trauma to the digit’s nail folds is described; the fungal culture grew Candida parapsilosis . Including our patient, Candida -associated longitudinal melanonychia striata has been described in four women and two men ranging in age from 40 to 79 years (median, 70 years) at diagnosis. The black streak, present from one month to one year (median, seven months), affected either a hand digit (five patients) or the great toe (one patient). Fungal organisms were visualized on either a potassium hydroxide preparation (one patient), pathologic evaluation of a nail plate specimen (three patients), or both (one patient). Culture grew Candida parapsilosis (two patients), Candida species (two patients), Candida albicans (one patient), and Candida tropicalis (one patient). All of the patients experienced clinical improvement after treatment. Topical treatment (5% amorolfine hydrochloride nail lacquer for two patients or modified Castellani paint and 1% clotrimazole cream for one man) or oral itraconazole (either as monotherapy for two women or combined with 5% amorolfine hydrochloride nail lacquer for one woman) was successfully used. Although the clinical presentation of fungal melanonychia can mimic subungual melanoma when it appears as a solitary black linear vertical nail plate streak, investigative studies--such as a potassium hydroxide preparation, nail plate pathology, nail matrix biopsy, and/or fungal culture--can be used to establish the diagnosis of Candida -associated longitudinal melanonychia striata and exclude the diagnosis of a pigmented melanocytic tumor.

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The prevalence of patients with chronic pain who display depressive symptoms is quite high, with depression potentially an integral component of chronic pain. Since the current subjective clinical diagnostic systems were not designed to assess depression in patients with chronic pain, they fail to adequately capture the nature of mood states of these patients. It is difficult to apply these assessment tools to segregate unipolar depression (MDD) from the demoralization inherent in chronic pain states. MDDScore™, a multivariate biomarker blood test for depression, was used to determine if it was possible to identify biomarker patterns consistent with major depressive disorder in multiple chronic pain states. Three study groups were analyzed, and included: (i) patients (n=93) with centralized Chronic Intractable Pain (CIP), (ii) patients (n=20) with chronic pain of diverse origin from Scripps Pain Clinic (SPC) and (iii) prospectively collected patients (n=28) with comorbid arthritis and depressive symptoms. A very distinct bimodal pattern was observed. Forty-nine of 93 CIP patients (52.7%), 18 of 28 (64.2%) of the arthritis patients, and 9 of 20 (45%) patients with chronic pain of diverse origin from Scripps Pain Clinic had MDDScores of ≥5. Thus, the biomarker panel could segregate patients into two major groups based upon MDDScores. These data suggest but not prove we can objectively identify chronic pain patients with a higher probability of comorbid major depression.Importantly, we can use the biomarkers on the MDDScore panel to gain insight into and gauge the residual (post-treatment) level of inflammation in these intensively treated patients. To this end, we determined and compared the serum concentrations of alpha-1 antitrypsin (A1AT), Myeloperoxidase (MPO) and soluble tumor necrosis factor receptor type 2 (sTNFR2) in each of the patient populations studied.