Changes In Response Properties Research Articles

Stimuli-Responsive Polymers at the Interface with Biology.

There has been growing interest in polymeric systems that break down or undergo property changes in response to stimuli. Such polymers can play important roles in biological systems, where they can be used to control the release of therapeutics, modulate imaging signals, actuate movement, or direct the growth of cells. In this Perspective, after discussing the most important stimuli relevant to biological applications, we will present a selection of recent exciting developments. The growing importance of stimuli-responsive polysaccharides will be discussed, followed by a variety of stimuli-responsive polymeric systems for the delivery of small molecule drugs and nucleic acids. Switchable polymers for the emerging area of therapeutic response measurement in theranostics will be described. Then, the diverse functions that can be achieved using hydrogels cross-linked covalently, as well as by various dynamic approaches will be presented. Finally, we will discuss some of the challenges and future perspectives for the field.

Temperature‐Responsive Polyoxometalates‐Based Materials: From Underlying Mechanism to Promising Applications

AbstractPolyoxometalates (POMs) are multifunctional anionic metal‐oxygen complexes with structural and electronic diversity, as well as tunable acid‐base and redox properties, resulting in their potential as building blocks for constructing temperature‐responsive polyoxometalates‐based materials (TRPMs). TRPMs represent a class of intelligent materials exhibiting property changes in response to temperature fluctuations, offering distinctive applications in various fields such as catalysis, medicine, sensors, imaging, and so on. Though many TRPMs are reported, a systematic review including recent advances is still absent. This review provides insights into recent advancements in temperature‐responsive mechanisms, nanostructure design strategies, and the characterization of TRPMs. Special emphasis is placed on enhancing the temperature‐responsive properties of TRPMs by incorporating POMs into suitable organic ligands, such as ionic liquid cations, deep eutectic solvent cations, cationic surfactants, and polymers. The incorporation of organic ligands with POMs not only enables temperature‐responsive phase transitions but also enhances other properties, such as catalyst selectivity and drug loading capacity, expanding TRPMs applications. Consequently, this review summarizes the applications of TRPMs in catalysis, drug delivery and release, and chemical sensing, as well as discusses future technological challenges. The in‐depth understanding of TRPMs may help in the design of TRPMs from the nanoscale, guiding and inspiring future development.

Nonpolar selective emission (NPSE) of carbonyl-bridged rhodols.

Polarity-responsive luminophores (PRLs), whose emission properties change in response to the polarity of the surrounding environment, are used for the fluorescence sensing of intracellular environments and various chemical compounds. Herein, we propose a concept called nonpolar selective emission (NPSE) for the development of a new PRL family. Unlike the conventional emission of PRLs, the NPSE luminophore can switch to a completely non-emissive state upon a slight increase in solvent polarity. The NPSE concept offers a new means of distinguishing between nonpolar and low-polarity environments. Moreover, the NPSE property is little affected by the viscosity of the surrounding medium. We demonstrate that NPSE dyes can be used as emission sensors for molecular gases. Furthermore, we discovered the potential use of NPSE dyes as a time-dependent security ink triggered by the volatilization of polar molecules.

Poster Session: The impact of retinal excitotoxic lesions on parallel visual streams in the ferret dorsal lateral geniculate nucleus.

Attesting to the relative strength of retinal inputs to the dorsal lateral geniculate nucleus (LGN) of the thalamus, in cats, acute retinal lesions erase responses of LGN neurons whose receptive fields fall within the retinal lesion projection zone (LPZ). Yet, thirty days later, these receptive fields appear to shift their representation to the immediate surround of the LPZ. However, little is known about whether LGN neurons in parallel streams are equally affected following retinal damage. Here, we asked whether changes in response properties of surviving LGN neurons depend on (1) their identity as either X/Y or ON/OFF cells, or (2) their receptive fields' positions relative to the LPZ. To test these hypotheses, we made retinal lesions by injecting kainic acid (KA) into one eye of ferrets and recorded from LGN neurons bilaterally in response to visual stimuli 7 days post-lesion. Area and eccentricities of retinal ganglion cell (RGC) loss in the retina were measured by RBPMS immunostaining. Relative eccentricities of recorded LGN neurons were based on electrode tracts. Our preliminary data suggest that RGC with large cell bodies are preserved in the lesioned eye. Additionally, we observed normal transient responses but altered sustained responses to flashing stimuli among contralateral responsive OFF LGN neurons. Together, these findings support the notion that acute KA lesions may differentially impact visual parallel processing streams at the surround of the LPZ in the LGN.

Descending Facilitation of Nociceptive Transmission From the Rostral Ventromedial Medulla Contributes to Hyperalgesia in Mice with Sickle Cell Disease

Sickle cell disease (SCD) is an inherited blood disorder that is associated with acute episodic and chronic pain. Mice with SCD have robust hyperalgesia mediated, in part, by sensitization of spinal dorsal horn neurons. However, underlying mechanisms are not fully understood. Since the rostral ventromedial medulla (RVM) is a major component of descending circuitry that modulates nociceptive transmission in the spinal cord, we examined if the RVM contributes to hyperalgesia in mice with SCD. Injection of lidocaine, but not vehicle, into the RVM eliminated mechanical and heat hyperalgesia in sickle (HbSS-BERK) mice without altering mechanical and heat sensitivity in naïve C57B mice. These data indicate that the RVM contributes to the maintenance of hyperalgesia in mice with SCD. In electrophysiological studies, we determined the changes in response properties of RVM neurons that might contribute to hyperalgesia in sickle mice. Recordings were made from single ON, OFF, and Neutral cells in the RVM of sickle and control (HbAA-BERK) mice. Spontaneous activity and responses of ON, OFF and Neutral cells evoked by heat (50 °C) and mechanical (26 g) stimuli applied to the hind paw were compared between sickle and control mice. Although there were no differences in the proportions of functionally-identified neurons or spontaneous activity between sickle and control mice, evoked responses of ON cells to heat and mechanical stimuli were increased approximately 3-fold in sickle mice as compared to control mice. Thus, the RVM contributes to hyperalgesia in sickle mice via a specific ON cell-dependent descending facilitation of nociceptive transmission.

In vivo characterization of cerebrovascular impairment induced by amyloid β peptide overload in glymphatic clearance system using swept-source optical coherence tomography.

Antiamyloid ( ) immunotherapy is a promising therapeutic strategy for Alzheimer's disease (AD) but generates large amounts of soluble peptides that could overwhelm the clearance pathway, leading to serious side effects. Direct implications of in glymphatic drainage transport for cerebral vasculature and tissue are not well known. Studies are needed to resolve this issue and pave the way to better monitoring abnormal vascular events that may occur in -modifying therapies for AD. The objective is to characterize the modification of cerebral vasculature and tissue induced by soluble abundantly present in the glymphatic clearance system. peptide was injected intracerebroventricularly and swept-source optical coherence tomography (SS-OCT) was used to monitor the progression of changes in the brain microvascular network and tissue in vivo over 14 days. Parameters reflecting vascular morphology and structure as well as tissue status were quantified and compared before treatment. Vascular perfusion density, vessel length, and branch density decreased sharply and persistently following peptide administration. In comparison, vascular average diameter and vascular tortuosity were moderately increased at the late stage of monitoring. Endpoint density gradually increased, and the global optical attenuation coefficient value decreased significantly over time. burden in the glymphatic system directly contributes to cerebrovascular structural and morphological abnormalities and global brain tissue damage, suggesting severe deleterious properties of soluble cerebrospinal fluid- . We also show that OCT can be used as an effective tool to monitor cerebrovascular dynamics and tissue property changes in response to therapeutic treatments in drug discovery research.

Technical note: Noninvasive monitoring of normal tissue radiation damage using spectral quantitative ultrasound spectroscopy.

While radiation therapy (RT) is a critical component of breast cancer therapy and is known to decrease overall local recurrence rates, recent studies have shown that normal tissue radiation damage may increase recurrence risk. Fibrosis is a well-known consequence of RT, but the specific sequence of molecular and mechanical changes induced by RT remains poorly understood. To improve cancer therapy outcomes, there is a need to understand the role of the irradiated tissue microenvironment in tumor recurrence. This study seeks to evaluate the use of spectral quantitative ultrasound (spectral QUS) for real time determination of the normal tissue characteristic radiation response and to correlate these results to molecular features in irradiated tissues. Murine mammary fat pads (MFPs) were irradiated to 20Gy, and spectral QUS was used to analyze tissue physical properties pre-irradiation as well as at 1, 5, and 10 days post-irradiation. Tissues were processed for scanning electron microscopy imaging as well as histological and immunohistochemical staining to evaluate morphology and structure. Tissue morphological and structural changes were observed non-invasively following radiation using mid-band fit (MBF), spectral slope (SS), and spectral intercept (SI) measurements obtained from spectral QUS. Statistically significant shifts in MBF and SI indicate structural tissue changes in real time, which matched histological observations. Radiation damage was indicated by increased adipose tissue density and extracellular matrix (ECM) deposition. Our findings demonstrate the potential of using spectral QUS to noninvasively evaluate normal tissue changes resulting from radiation damage. This supports further pre-clinical studies to determine how the tissue microenvironment and physical properties change in response to therapy, which may be important for improving treatment strategies.

In vitro Quality Assessments of Perfluorocarbon Nanoemulsions for Near-infrared Fluorescence Imaging of Inflammation in Preclinical Models.

Tracking macrophages by non-invasive molecular imaging can provide useful insights into the immunobiology of inflammatory disorders in preclinical disease models. Perfluorocarbon nanoemulsions (PFC-NEs) have been well documented in their ability to be taken up by macrophages through phagocytosis and serve as 19F magnetic resonance imaging (MRI) tracers of inflammation in vivo and ex vivo. Incorporation of near-infrared fluorescent (NIRF) dyes in PFC-NEs can help monitor the spatiotemporal distribution of macrophages in vivo during inflammatory processes, using NIRF imaging as a complementary methodology to MRI. Here, we discuss in depth how both colloidal and fluorescence stabilities of the PFC-NEs are essential for successful and reliable macrophage tracking in vivo and for their detection in excised tissues ex vivo by NIRF imaging. Furthermore, PFC-NE quality assures NIRF imaging reproducibility and reliability across preclinical studies, providing insights into inflammation progression and therapeutic response. Previous studies focused on assessments of colloidal property changes in response to stress and during storage as a means of quality control. We recently focused on the joint evaluation of both colloidal and fluorescence properties and their relationship to NIRF imaging outcomes. In this protocol, we summarize the key assessments of the fluorescent dye-labeled nanoemulsions, which include long-term particle size distribution monitoring as the measure of colloidal stability and monitoring of the fluorescence signal. Due to its simplicity and reproducibility, our protocols are easy to adopt for researchers to assess the quality of PFC-NEs for in vivo NIRF imaging applications.

Recent advances in responsive membrane functionalization approaches and applications

ABSTRACT In recent years, significant advances have been made in the field of functionalized membranes. With the functionalization using various materials, such as polymers and enzymes, membranes can exhibit property changes in response to an environmental stimulation, such as heat, light, ionic strength, or pH. The resulting responsive nature allows for an increased breadth of membrane uses, due to the developed functionalization properties, such as smart-gating filtration for size-selective water contaminant removal, self-cleaning antifouling surfaces, increased scalability options, and highly sensitive molecular detection. In this review, new advances in both fabrication and applications of functionalized membranes are reported and summarized, including temperature-responsive, pH-responsive, light-responsive, enzyme-functionalized, and two-dimensional material-functionalized membranes. Specific emphasis was given to the most recent technological improvements, current limitations, advances in characterization techniques, and future directions for the field of functionalized membranes.

4D Printed Multifunctional Composites with Cooling‐Rate Mediated Tunable Shape Morphing

AbstractMultifunctional composites can accomplish multiple tasks such as shape morphing, sensing, and load bearing using a single structure. Smart materials including liquid crystal elastomers (LCE) and shape memory polymers (SMP) have long been used as the primary components of multifunctional composites because of their shape and property changes in response to external stimuli. However, LCEs can generate rapid and reversible shape changes but are soft and require a constant temperature to retain their deformed shape; SMPs have favorable mechanical properties but few can achieve reversible actuations. Moreover, both LCEs and SMPs have limited capability for tunable shape morphing. Multi‐material 3D printing of smart materials, also known as 4D printing, has seen significant advances enabling the fabrication of composites with novel functionality. In this work, 4D printing is leveraged to create an LCE‐SMP composite that can achieve not only rapid and reversible shape changes, but also cooling‐rate regulated tunable shape morphing. The latter is achieved by harnessing the distinct time‐dependent thermomechanical properties of LCEs and SMPs. Furthermore, the composite has a high stiffness at low temperature to support heavy loads. The LCE‐SMP composite hence offers a novel approach to achieve tunable shape morphing for future engineering applications.

Distinct response properties between the FFA to faces and the PPA to houses.

IntroductionThe object recognition system involves both selectivity to specific object category and invariance to changes in low‐level visual features. Mounting neuroimaging evidence supports that brain areas in the ventral temporal cortex, such as the FFA and PPA, respond preferentially to faces and houses, respectively. However, how regions in human ventral temporal cortex partitioned and functionally organized to selectively and invariantly respond to different object categories remains unclear. What are the changes of response properties at the intersection of adjacent but distinctively‐selective regions?MethodHere, we conducted an fMRI study and three‐pronged analyses to compare the brain mapping relationships between the FFA to faces and the PPA to houses. Specifically, we examined: 1) the response properties of object selectivity to the preferred category; 2) the response properties of invariance to contrast and a concurrently presented non‐preferred category; 3) whether there are asymmetrical changes of response properties across the boundary from the FFA to PPA versus from the PPA to FFA.ResultsWe found that the response properties of FFA are highly selective and reliably invariant, whereas the responses of PPA vary with the image contrast and concurrently presented face. Moreover, the response properties across the boundary between the FFA and PPA are asymmetrical from face‐selective to house‐selective relative to from house‐selective to face‐selective.ConclusionsThese results convergently revealed distinct response properties between the FFA to faces and the PPA to houses, implying a combination of spatially discrete domain‐specific and relatively distributed domain‐general organization mapping in human ventral temporal cortex.

Assessing multimodal optical imaging of perfusion in burn wounds

A critical need exists for early, accurate diagnosis of burn wound severity to help identify the course of treatment and outcome of the wound. Laser speckle imaging (LSI) is a promising blood perfusion imaging approach, but it does not account for changes in tissue optical properties that can occur with burn wounds, which are highly dynamic environments. Here, we studied optical property dynamics following burn injury and debridement and the associated impact on interpretation of LSI measurements of skin perfusion. We used spatial frequency domain imaging (SFDI) measurements of tissue optical properties to study the impact of burn-induced changes in these properties on LSI measurements. An established preclinical porcine model of burn injury was used (n = 8). SFDI and LSI data were collected from burn wounds of varying severity. SFDI measurements demonstrate that optical properties change in response to burn injury in a porcine model. We then apply theoretical modeling to demonstrate that the measured range of optical property changes can affect the interpretation of LSI measurements of blood flow, but this effect is minimal for most of the measured data. Collectively, our results indicate that, even with a dynamic burn wound environment, blood-flow measurements with LSI can serve as an appropriate strategy for accurate assessment of burn severity.

Soft, Wirelessly Powered Humidity Sensor Based on SnO2 Nanowires for Wireless/Wearable Sensor Application.

Humidity, along with temperature, is one of the most important environmental variables in people’s lives. The control of humidity is an important matter that is related to material properties and stability in various industries, as well as basic living. In order to detect humidity, changes in the physical, chemical, and electrical properties of materials related to humidity are used, and studies using various methods are conducted. In this study, a field-effect transistor (FET) device was fabricated on a soft polymer substrate with SnO2 nanowires (NWs), whose electrical properties change in response to water molecules. The SnO2 NWs, synthesized by chemical vapor deposition (CVD), were transferred onto a polymer substrate, using a sliding transfer method. The NW FET device, which was connected to an aluminum (Al)-based radio frequency (RF) receiving antenna, was wirelessly operated as a humidity sensor, based on the change in electrical properties of SnO2 NWs according to the relative humidity (RH). It was configured with a wireless antenna and light emitting diode (LED) indicator to implement a soft wirelessly powered humidity sensor that senses high RH and is expected to be used as a wearable electronic/sensor in the future.

Transient swelling behaviour of dual stimuli sensitive nanocomposite hydrogels

Smart nanocomposite hydrogels can undergo large deformation under external stimuli. Several coupled physical processes simultaneously affect the transient swelling behaviour of pH and temperature-sensitive hydrogels. Besides, the hydrogel properties change in response to the external stimuli in the presence of nanoparticles, which affect its transient deformation and swelling behaviour. This work focused on transient swelling modeling of pH and temperature-sensitive polymer/clay nanocomposite hydrogels. The time-dependent processes were considered simultaneously with material properties updating in each time-step during the finite element procedure. A set of experiments was designed to evaluate the numerical solving results in the free and constrained swelling conditions. The results illustrate that the proposed developed model successfully predicts the transient swelling behaviour of pH and temperature-sensitive either for hydrogels or nanocomposite hydrogel counterparts, which can offer a guideline to the abundant usage of these soft materials.

Stimuli-Responsive Polymer Systems—Recent Manufacturing Techniques and Applications

Stimuli-responsive polymer systems can be defined as functional materials that show physical or chemical property changes in response to external stimuli, such as temperature, radiation, chemical agents, pH, mechanical stress, and electric and magnetic fields [...].

Depiction of Oral Tumor-Induced Trigeminal Afferent Responses Using Single-Fiber Electrophysiology

Considerable gap in knowledge exists about the mechanisms by which oral tumors regulate peripheral sensory fibers to produce pain and altered sensations. To address this gap, we used a murine model of oral squamous cell carcinoma (OSCC) of the tongue to investigate changes in response properties of trigeminal afferent neurons. Using this model, we developed an ex vivo method for single neuron recordings of the lingual nerve from isolated tongue tissue. Our data demonstrated that the tongue tumor produced increased spontaneous firing of lingual fibers compared to control as well as produced mechanical hypersensitivity and reduced von Frey thresholds of C- and A-slow-high-threshold mechanoreceptors (HTMR) fibers but had no effect on C-LTMR, A-slow-LTMR and A-fast lingual fibers. Mechanically-insensitive fibers were also detected in lingual afferents of the control group, that were significantly decreased in tumor-bearing preparations. Collectively, using single fiber electrophysiology of lingual sensory fibers, we show that human OSCC tumors sensitize peripheral trigeminal nerve terminals, providing a unique opportunity to study mechanisms of oral cancer pain.

Magnetic thermosensitive micelles with upper critical solution temperature for NIR triggered drug release.

Smart micelles which undergo dramatic property changes in response to temperature have aroused extensive interest in specific cancer therapy. To date, studies on thermosensitive polymers have mainly focused on lower critical solution temperature (LCST) polymers. Materials with upper critical solution temperature (UCST) which can swell and disassemble at elevated temperatures have much less been documented, although they have been reported to be ideal carriers for quick and complete drug release upon applying a stimulus. Here, magnetic micelles with UCST are developed for doxorubicin (DOX) delivery. Hydrophobic Fe3O4 magnetic nanoparticles with a particle size of 8 nm are fabricated and enveloped in an amphiphilic polymer, poly(AAm-co-AN)-g-PEG (PAAP), to form UCST micelles (Fe3O4@PAAP). The resulting micelles exhibit excellent photothermal effects and burst drug release in response to near infrared (NIR) laser irradiation. The in vitro and in vivo antitumor experiments indicate that DOX-Fe3O4@PAAP micelles can significantly enhance the therapeutic effect upon NIR light irradiation. A novel thermosensitive platform is thus offered for in situ drug release and combined photothermal-chemotherapy, holding a favorable prospect for cancer therapy.

Soil Chemical Property Changes in Response to Long‐Term Pineapple Cultivation in Costa Rica

Core Ideas Soil organic C was lower under pineapple cultivation than in an adjacent pasture and secondary forest. Soil organic C did not differ between 7‐ and 20‐yr‐old pineapple fields. Soil pH and base cations were lower in a 20‐ than in a 7‐yr‐old pineapple field, pasture, and forest. Anion exchange capacities were larger in soils under pineapple cultivation than in pasture soils. Pineapple cultivation may require increased liming rates to help maintain long‐term soil quality. Pineapple [Ananas comosus (L.) Merr.] has been cultivated in Costa Rica for decades on land previously under forest and pasture vegetation. A pineapple plantation in Costa Rica was chosen to investigate the impact of long‐term pineapple cultivation on soil chemical properties. Soil samples were collected at pineapple sites under cultivation for 7 and 20 yr, as well as in an adjacent pasture and secondary forest. Samples were analyzed for extractable nutrients, total C and N, and cation and anion exchange capacities (CEC and AEC, respectively). Soil organic carbon (SOC) and soil N concentrations did not differ (P > 0.05) between the 7‐ and 20‐yr‐old pineapple sites nor between the pasture and forest sites in the top 20 cm. However, the average SOC concentration in the pasture and forest sites was 1.5 times greater (P < 0.05) than that in the pineapple sites. Soil AEC was 3.5 times greater (P < 0.05) in the top 10 cm of both pineapple sites than in the pasture. The 20‐yr‐old pineapple site, which had a soil pH of 4.1, had 2 to 13 times greater (P < 0.05) exchangeable acidity and 2 to 5 times lower base cation concentrations in the top 20 cm than the 7‐yr‐old pineapple, pasture, and forest sites. The greater acidity and lower base cation concentrations in the older pineapple site suggest that agronomic management practices may need to be adjusted to minimize negative changes in soil chemical properties and help maintain future soil productivity.

Colitis-induced alterations in response properties of visceral nociceptive neurons in the rat caudal medulla oblongata and their modulation by 5-HT3 receptor blockade

There is considerable clinical and experimental evidence that intestinal inflammation is associated with altered visceral nociceptive processing in the spinal cord and brain, but the underlying neuronal mechanisms, especially acting at the supraspinal level, remain unclear. Considering that the caudal ventrolateral medulla (CVLM) and the nucleus tractus solitarius (NTS) are the first sites for supraspinal processing of visceral pain signals, in the present study we evaluated the experimental colitis-induced changes in response properties of CVLM and NTS medullary neurons to noxious colorectal distension (CRD) in urethane-anesthetized adult male Wistar rats. To determine if gut inflammation alters the 5-HT3 receptor-dependent modulation of visceral pain-related CVLM and NTS cells, we examined the effects of intravenously administered selective 5-HT3 antagonist granisetron on ongoing and CRD-evoked activity of CVLM and NTS neurons in healthy control and colitic animals. In the absence of colonic pathology, the CVLM neurons were more excited by noxious CRD that the NTS cells, which demonstrated a greater tendency to be inhibited by the stimulation. The difference was eliminated after the development of colitis due to the increase in the proportion of CRD-excited neurons in both medullary regions associated with enhanced magnitude of the neuronal nociceptive responses. Intravenous granisetron (1 or 2 mg/kg) produced the dose-dependent suppression of the ongoing and evoked firing of CRD-excited cells within both the CVLM and NTS in normal conditions as well as was able to substantially reduce excitability of the caudal medullary neurons in the presence of colonic inflammation, arguing for the potential efficacy of the 5-HT3 receptor blockade with granisetron against both acute and inflammatory abdominal pain. Taken together, the data obtained can contribute to a deeper understanding of supraspinal serotonergic mechanisms responsible for the persistence of visceral hypersensitivity and hyperalgesia triggered by colonic inflammation.

Overexpression of µ-Opioid Receptors in Peripheral Afferents, but Not in Combination with Enkephalin, Decreases Neuropathic Pain Behavior and Enhances Opioid Analgesia in Mouse

The current study used recombinant herpes simplex virus type I to increase expression of µ-opiate receptors and the opioid ligand preproenkephalin in peripheral nerve fibers in a mouse model of neuropathic pain. It was predicted that viral vector delivery of a combination of genes encoding the µ-opioid receptor and preproenkephalin would attenuate neuropathic pain and enhance opioid analgesia. The behavioral effects would be paralleled by changes in response properties of primary afferent neurons. Recombinant herpes simplex virus type 1 containing cDNA sequences of the µ-opioid receptor, human preproenkephalin, a combination, or Escherichia coli lacZ gene marker (as a control) was used to investigate the role of peripheral opioids in neuropathic pain behaviors. Inoculation with the µ-opioid receptor viral vector (n = 13) reversed mechanical allodynia and thermal hyperalgesia and produced leftward shifts in loperamide (ED50 = 0.6 ± 0.2 mg/kg vs. ED50 = 0.9 ± 0.2 mg/kg for control group, n = 8, means ± SD) and morphine dose-response curves (ED50 = 0.3 ± 0.5 mg/kg vs. ED50 = 1.1 ± 0.1 mg/kg for control group). In µ-opioid receptor viral vector inoculated C-fibers, heat-evoked responses (n = 12) and ongoing spontaneous activity (n = 18) were decreased after morphine application. Inoculation with both µ-opioid receptor and preproenkephalin viral vectors did not alter mechanical and thermal responses. Increasing primary afferent expression of opioid receptors can decrease neuropathic pain-associated behaviors and increase systemic opioid analgesia through inhibition of peripheral afferent fiber activity.